Rank-Similarity Measures for Comparing Gene Prioritizations: A Case Study in Autism.

We discuss the challenge of comparing three gene prioritization methods: network propagation, integer linear programming rank aggregation (RA), and statistical RA. These methods are based on different biological categories and estimate disease-gene association. Previously proposed comparison schemes are based on three measures of performance: receiver operating curve, area under the curve, and median rank ratio. Although they may capture important aspects of gene prioritization performance, they may fail to capture important differences in the rankings of individual genes. We suggest that comparison schemes could be improved by also considering recently proposed measures of similarity between gene rankings. We tested this suggestion on comparison schemes for prioritizations of genes associated with autism that were obtained using brain- and tissue-specific data. Our results show the effectiveness of our measures of similarity in clustering brain regions based on their relevance to autism.

EDoP Distance Between Sets of Incomplete Permutations: Application to Bacteria Classification Based on Gene Order.

In this work, we extend measures of distance between permutations to support incomplete permutations. Modeling and comparing incomplete permutations are a challenging computational problem of practical importance in many applications in bioinformatics and social science. We show that the proposed distance measure admits a closed-form expression and can be efficiently computed on sets of permutations involving several missing elements. We demonstrate the proposed method on the classification of bacteria from different phyla based on gene order.

Fontan Surgical Planning: Previous Accomplishments, Current Challenges, and Future Directions.

The ultimate goal of Fontan surgical planning is to provide additional insights into the clinical decision-making process. In its current state, surgical planning offers an accurate hemodynamic assessment of the pre-operative condition, provides anatomical constraints for potential surgical options, and produces decent post-operative predictions if boundary conditions are similar enough between the pre-operative and post-operative states. Moving forward, validation with post-operative data is a necessary step in order to assess the accuracy of surgical planning and determine which methodological improvements are needed. Future efforts to automate the surgical planning process will reduce the individual expertise needed and encourage use in the clinic by clinicians. As post-operative physiologic predictions improve, Fontan surgical planning will become an more effective tool to accurately model patient-specific hemodynamics.

Hemodynamic Impact of Superior Vena Cava Placement in the Y-Graft Fontan Connection.

BACKGROUND: A Fontan Y-shaped graft using a commercially available aortoiliac graft has been used to connect the inferior vena cava (IVC) to the pulmonary arteries. This modification of the Fontan procedure seeks to improve hepatic flow distribution (HFD) to the lungs. However, patient-specific anatomical restrictions might limit the space available for graft placement. Altering the superior vena cava (SVC) positioning is hypothesized to provide more space for an optimal connection, avoiding caval flow collision. Computational modeling tools were used to retrospectively study the effect of SVC placement on Y-graft hemodynamics. METHODS: Patient-specific anatomies (N = 10 patients) and vessel flows were reconstructed from retrospective cardiac magnetic resonance (CMR) images after Fontan Y-graft completion. Alternative geometries were created using a virtual surgery environment, altering the SVC position and the offset in relation to the Y-graft branches. Geometric characterization and computational fluid dynamics simulations were performed. Hemodynamic factors (power loss and HFD) were computed. RESULTS: Patients with a higher IVC return showed less sensitivity to SVC positioning. Patients with low IVC flow showed varied HFD results, depending on SVC location. Balanced HFD values (50% to each lung) were obtained when the SVC lay completely between the Y-graft branches. The effect on power loss was patient specific. CONCLUSIONS: SVC positioning with respect to the Y-graft affects HFD, especially in patients with lower IVC flow. Careful positioning of the SVC at the time of a bidirectional Glenn (BDG) procedure based on patient-specific anatomy can optimize the hemodynamics of the eventual Fontan completion.

Surgical planning of the total cavopulmonary connection: robustness analysis.

In surgical planning of the Fontan connection for single ventricle physiologies, there can be differences between the proposed and implemented options. Here, we developed a surgical planning framework that help determine the best performing option and ensures that the results will be comparable if there are slight geometrical variations. Eight patients with different underlying anatomies were evaluated in this study; surgical variations were created for each connection by changing either angle, offset or baffle diameter. Computational fluid dynamics were performed and the energy efficiency (indexed power loss-iPL) and hepatic flow distribution (HFD) computed. Differences with the original connection were evaluated: iPL was not considerably affected by the changes in geometry. For HFD, the single superior vena cava (SVC) connections presented less variability compared to the other anatomies. The Y-graft connection was the most robust overall, while the extra-cardiac connections showed dependency to offset. Bilateral SVC and interrupted inferior vena cava with azygous continuation showed high variability in HFD. We have developed a framework to assess the robustness of a surgical option for the TCPC; this will be useful to assess the most complex cases where pre-surgery planning could be most beneficial to ensure an efficient and robust hemodynamic performance.

Grouper: a compact, streamable triangle mesh data structure.

We present Grouper: an all-in-one compact file format, random-access data structure, and streamable representation for large triangle meshes. Similarly to the recently published SQuad representation, Grouper represents the geometry and connectivity of a mesh by grouping vertices and triangles into fixed-size records, most of which store two adjacent triangles and a shared vertex. Unlike SQuad, however, Grouper interleaves geometry with connectivity and uses a new connectivity representation to ensure that vertices and triangles can be stored in a coherent order that enables memory-efficient sequential stream processing. We present a linear-time construction algorithm that allows streaming out Grouper meshes using a small memory footprint while preserving the initial ordering of vertices. As a part of this construction, we show how the problem of assigning vertices and triangles to groups reduces to a well-known NP-hard optimization problem, and present a simple yet effective heuristic solution that performs well in practice. Our array-based Grouper representation also doubles as a triangle mesh data structure that allows direct access to vertices and triangles. Storing only about two integer references per triangle--i.e., less than the three vertex references stored with each triangle in a conventional indexed mesh format--Grouper answers both incidence and adjacency queries in amortized constant time. Our compact representation enables data-parallel processing on multicore computers, instant partitioning and fast transmission for distributed processing, as well as efficient out-of-core access. We demonstrate the versatility and performance benefits of Grouper using a suite of example meshes and processing kernels.

Haemodynamic comparison of a novel flow-divider Optiflo geometry and a traditional total cavopulmonary connection.

OBJECTIVES: The total cavopulmonary connection (TCPC), the current palliation of choice for single-ventricle heart defects, is typically created with a single cylindrical tunnel or conduit routing inferior vena caval (IVC) flow to the pulmonary arteries. Previous studies have shown the haemodynamic efficiency of the TCPC to be sub-optimal due to the collision of vena caval flow, thus placing an extra energy burden on the single ventricle. The use of a bifurcated graft as the Fontan baffle (i.e. the 'Optiflo') has previously been proposed on the basis of theoretically improved flow efficiency; however, anatomical constraints may limit its effectiveness in some patients. METHODS: In this study, an alternative approach to flow bifurcation is proposed, where a triangular insert is placed at the distal end of the IVC graft. The proof of concept for this design is demonstrated in two steps: first, determining the optimal insert size at a fixed Fontan graft size through a parametric study; then, characterizing the efficiency as a function of graft size when compared with a TCPC control. TCPC power loss and IVC flow distribution were the primary metrics of interest and were evaluated under both resting and simulated exercise conditions using an in-house computational fluid dynamics solver. RESULTS: Results demonstrated that there was an optimal insert size that improved efficiency compared with the TCPC. For an 18-mm Fontan baffle, TCPC power loss was 4.1 vs 3.7 mW with the optimal flow-divider. The optimal insert was then scaled up for a 20-mm graft, with a similar reduction in power loss observed. Flow distribution results were inconsistent, based on sensitivity to the placement of the insert within the baffle. CONCLUSION: This study demonstrated proof of concept that the flow-divider has the potential to reduce power loss and streamline IVC flow through the TCPC. An appropriate size for the insert in proportion to the Fontan baffle size was identified that reduced losses compared with a TCPC control under both resting and simulated exercise flow conditions.

Accuracy of a mitral valve segmentation method using J-splines for real-time 3D echocardiography data.

Patient-specific models of the heart's mitral valve (MV) exhibit potential for surgical planning. While advances in 3D echocardiography (3DE) have provided adequate resolution to extract MV leaflet geometry, no study has quantitatively assessed the accuracy of their modeled leaflets vs. a ground-truth standard for temporal frames beyond systolic closure or for differing valvular dysfunctions. The accuracy of a 3DE-based segmentation methodology based on J-splines was assessed for porcine MVs with known 4D leaflet coordinates within a pulsatile simulator during closure, peak closure, and opening for a control, prolapsed, and billowing MV model. For all time points, the mean distance error between the segmented models and ground-truth data were 0.40 ± 0.32 mm, 0.52 ± 0.51 mm, and 0.74 ± 0.69 mm for the control, flail, and billowing models. For all models and temporal frames, 95% of the distance errors were below 1.64 mm. When applied to a patient data set, segmentation was able to confirm a regurgitant orifice and post-operative improvements in coaptation. This study provides an experimental platform for assessing the accuracy of an MV segmentation methodology at phases beyond systolic closure and for differing MV dysfunctions. Results demonstrate the accuracy of a MV segmentation methodology for the development of future surgical planning tools.

Simulating hemodynamics of the Fontan Y-graft based on patient-specific in vivo connections.

BACKGROUND: Using a bifurcated Y-graft as the Fontan baffle is hypothesized to streamline and improve flow dynamics through the total cavopulmonary connection (TCPC). This study conducted numerical simulations to evaluate this hypothesis using postoperative data from 5 patients. METHODS: Patients were imaged with cardiac magnetic resonance or computed tomography after receiving a bifurcated aorto-iliac Y-graft as their Fontan conduit. Numerical simulations were performed using in vivo flow rates, as well as 2 levels of simulated exercise. Two TCPC models were virtually created for each patient to serve as the basis for hemodynamic comparison. Comparative metrics included connection flow resistance and inferior vena caval flow distribution. RESULTS: Results demonstrate good hemodynamic outcomes for the Y-graft options. The consistency of inferior vena caval flow distribution was improved over TCPC controls, whereas the connection resistances were generally no different from the TCPC values, except for 1 case in which there was a marked improvement under both resting and exercise conditions. Examination of the connection hemodynamics as they relate to surgical Y-graft implementation identified critical strategies and modifications that are needed to potentially realize the theoretical efficiency of such bifurcated connection designs. CONCLUSIONS: Five consecutive patients received a Y-graft connection to complete their Fontan procedure with positive hemodynamic results. Refining the surgical technique for implementation should result in further energetic improvements that may help improve long-term outcomes.

Comparing pre- and post-operative Fontan hemodynamic simulations: implications for the reliability of surgical planning.

Virtual modeling of cardiothoracic surgery is a new paradigm that allows for systematic exploration of various operative strategies and uses engineering principles to predict the optimal patient-specific plan. This study investigates the predictive accuracy of such methods for the surgical palliation of single ventricle heart defects. Computational fluid dynamics (CFD)-based surgical planning was used to model the Fontan procedure for four patients prior to surgery. The objective for each was to identify the operative strategy that best distributed hepatic blood flow to the pulmonary arteries. Post-operative magnetic resonance data were acquired to compare (via CFD) the post-operative hemodynamics with predictions. Despite variations in physiologic boundary conditions (e.g., cardiac output, venous flows) and the exact geometry of the surgical baffle, sufficient agreement was observed with respect to hepatic flow distribution (90% confidence interval-14 ± 4.3% difference). There was also good agreement of flow-normalized energetic efficiency predictions (19 ± 4.8% error). The hemodynamic outcomes of prospective patient-specific surgical planning of the Fontan procedure are described for the first time with good quantitative comparisons between preoperatively predicted and postoperative simulations. These results demonstrate that surgical planning can be a useful tool for single ventricle cardiothoracic surgery with the ability to deliver significant clinical impact.

Preliminary clinical experience with a bifurcated Y-graft Fontan procedure--a feasibility study.

OBJECTIVE: Optimizing flow and diminishing power loss in the Fontan circuit can improve hemodynamic efficiency, potentially improving the long-term outcomes. Computerized modeling has predicted improved energetics with a Y-graft Fontan. METHODS: From August to December 2010, 6 consecutive children underwent completion Fontan (n=3) or Fontan revision (n=3) using a bifurcated polytetrafluoroethylene Y-graft (18×9×9 mm in 2, 20×10×10 mm in 4) connecting the inferior vena cava to the right and left pulmonary arteries with separate graft limbs. The patents underwent magnetic resonance imaging (n=5) or computed tomography (n=1). Computational fluid dynamics assessed Fontan hemodynamics, power loss, and inferior vena cava flow splits to the branch pulmonary arteries. The clinical parameters were compared with those from 12 patients immediately preceding the present series who had undergone a lateral Fontan procedure. RESULTS: Despite longer crossclamp and bypass times (not statistically significant), the Y-graft Fontan patients had postoperative courses similar to those of the conventional Fontan patients. Other than 2 early readmissions for pleural effusions managed with diuretics, at 6 to 12 months of follow-up (mean, 8 months), all 6 patients had done well. Postoperative flow modeling demonstrated a balanced distribution of inferior vena cava flow to both pulmonary arteries with minimal flow disturbance. Improvements in hemodynamics and efficiency were noted when the Y-graft branches were anastomosed distally and aligned tangentially with the branch pulmonary arteries. CONCLUSIONS: The present preliminary surgical experience has demonstrated the clinical feasibility of the bifurcated Y-graft Fontan. Computational fluid dynamics showed acceptable hemodynamics with low calculated power losses and a balanced distribution of inferior vena cava flow to the pulmonary arteries as long as the branch grafts were anastomosed distally.

Individualized computer-based surgical planning to address pulmonary arteriovenous malformations in patients with a single ventricle with an interrupted inferior vena cava and azygous continuation.

OBJECTIVE: Pulmonary arteriovenous malformations caused by abnormal hepatic flow distribution can develop in patients with a single ventricle with an interrupted inferior vena cava. However, preoperatively determining the hepatic baffle design that optimizes hepatic flow distribution is far from trivial. The current study combines virtual surgery and numeric simulations to identify potential surgical strategies for patients with an interrupted inferior vena cava. METHODS: Five patients with an interrupted inferior vena cava and severe pulmonary arteriovenous malformations were enrolled. Their in vivo anatomies were reconstructed from magnetic resonance imaging (n = 4) and computed tomography (n = 1), and alternate virtual surgery options (intracardiac/extracardiac, Y-grafts, hepato-to-azygous shunts, and azygous-to-hepatic shunts) were generated for each. Hepatic flow distribution was assessed for all options using a fully validated computational flow solver. RESULTS: For patients with a single superior vena cava (n = 3), intracardiac/extracardiac connections proved dangerous, because even a small left or right offset led to a highly preferential hepatic flow distribution to the associated lung. The best results were obtained with either a Y-graft spanning the Kawashima to split the flow or hepato-to-azygous shunts to promote mixing. For patients with bilateral superior vena cavae (n = 2), results depended on the balance between the left and right superior inflows. When those were equal, connecting the hepatic baffle between the superior vena cavae performed well, but other options should be pursued otherwise. CONCLUSIONS: This study demonstrates how virtual surgery environments can benefit the clinical community, especially for patients with a single ventricle with an interrupted inferior vena cava. Furthermore, the sensitivity of the optimal baffle design to the superior inflows underscores the need to characterize both preoperative anatomy and flows to identify the best option.

Ringing: frugal subdivision of curves and surfaces.

Ringing reduces the working memory needed during the rendering of subdivision curves, surfaces, and animations. For example, it only stores 4D vertices when rendering the dth level of subdivision of a polygon using four-point, cubic, or quintic B-spline subdivision masks. Ringing can be used on CPUs and GPUs.

Correction of pulmonary arteriovenous malformation using image-based surgical planning.

The objectives of this study were to develop an image-based surgical planning framework that 1) allows for in-depth analysis of pre-operative hemodynamics by the use of cardiac magnetic resonance and 2) enables surgeons to determine the optimum surgical scenarios before the operation. This framework is tailored for applications in which post-operative hemodynamics are important. In particular, it is exemplified here for a Fontan patient with severe left pulmonary arteriovenous malformations due to abnormal hepatic flow distribution to the lungs. Patients first undergo cardiac magnetic resonance for 3-dimensional anatomy and flow reconstruction. After analysis of the pre-operative flow fields, the 3-dimensional anatomy is imported into an interactive surgical planning interface for the surgeon to virtually perform multiple surgical scenarios. Associated hemodynamics are predicted by the use of a fully validated computational fluid dynamic solver. Finally, efficiency metrics (e.g., pressure decrease and hepatic flow distribution) are weighted against surgical feasibility to determine the optimal surgical option.

Patient-specific surgical planning and hemodynamic computational fluid dynamics optimization through free-form haptic anatomy editing tool (SURGEM).

The first version of an anatomy editing/surgical planning tool (SURGEM) targeting anatomical complexity and patient-specific computational fluid dynamics (CFD) analysis is presented. Novel three-dimensional (3D) shape editing concepts and human-shape interaction technologies have been integrated to facilitate interactive surgical morphology alterations, grid generation and CFD analysis. In order to implement "manual hemodynamic optimization" at the surgery planning phase for patients with congenital heart defects, these tools are applied to design and evaluate possible modifications of patient-specific anatomies. In this context, anatomies involve complex geometric topologies and tortuous 3D blood flow pathways with multiple inlets and outlets. These tools make it possible to freely deform the lumen surface and to bend and position baffles through real-time, direct manipulation of the 3D models with both hands, thus eliminating the tedious and time-consuming phase of entering the desired geometry using traditional computer-aided design (CAD) systems. The 3D models of the modified anatomies are seamlessly exported and meshed for patient-specific CFD analysis. Free-formed anatomical modifications are quantified using an in-house skeletization based cross-sectional geometry analysis tool. Hemodynamic performance of the systematically modified anatomies is compared with the original anatomy using CFD. CFD results showed the relative importance of the various surgically created features such as pouch size, vena cave to pulmonary artery (PA) flare and PA stenosis. An interactive surgical-patch size estimator is also introduced. The combined design/analysis cycle time is used for comparing and optimizing surgical plans and improvements are tabulated. The reduced cost of patient-specific shape design and analysis process, made it possible to envision large clinical studies to assess the validity of predictive patient-specific CFD simulations. In this paper, model anatomical design studies are performed on a total of eight different complex patient specific anatomies. Using SURGEM, more than 30 new anatomical designs (or candidate configurations) are created, and the corresponding user times presented. CFD performances for eight of these candidate configurations are also presented.

Anatomically realistic patient-specific surgical planning of complex congenital heart defects using MRI and CFD.

Single ventricle congenital heart defects, which are characterized by cyanotic mixing between the oxygenated and de-oxygenated blood, afflict 2 per every 1000 live births. These defects are surgically treated by connecting the superior and inferior vena cava to the pulmonary arteries. However, such a configuration (also known as the total cavopulmonary connection), results in high energy losses and therefore the optimization of this connection prior to the surgery could significantly improve post-operative performance. In this paper, a surgical planning framework is proposed. It is exemplified on a patient with pre and post surgical MRI data. A pediatric surgeon performed a "virtual surgery" on the reconstruction of the patient's anatomy prior to the actual surgery. Post-operative hemodynamics in the virtually designed post-surgical anatomy and in the actual one are computed using computational fluid dynamics and compared to each other. This framework provides the surgeon to envision numerous scenarios of possible surgical options, and accordingly predict the post operative hemodynamics.

CST: constructive solid trimming for rendering BReps and CSG.

Abstract-To eliminate the need to evaluate the intersection curves in explicit representations of surface cutouts or of trimmed faces in BReps of CSG solids, we advocate using Constructive Solid Trimming (CST). A CST face is the intersection of a surface with a Blist representation of a trimming CSG volume. We propose a new GPU-based CSG rendering algorithm that trims the boundary of each primitive using a Blist of its active zone. This approach is faster than the previously reported Blister approach, eliminates occasional speckles of wrongly colored pixels, and provides additional capabilities: painting on surfaces, rendering semitransparent CSG models, and highlighting selected features in the BReps of CSG models.

Advections with significantly reduced dissipation and diffusion.

Back and Forth Error Compensation and Correction (BFECC) was recently developed for interface computation using a level set method. We show that BFECC can be applied to reduce dissipation and diffusion encountered in a variety of advection steps, such as velocity, smoke density, and image advections on uniform and adaptive grids and on a triangulated surface. BFECC can be implemented trivially as a small modification of the first-order upwind or semi-Lagrangian integration of advection equations. It provides second-order accuracy in both space and time. When applied to level set evolution, BFECC reduces volume loss significantly. We demonstrate the benefits of this approach on image advection and on the simulation of smoke, bubbles in water, and the highly dynamic interaction between water, a solid, and air. We also apply BFECC to dye advection to visualize vector fields.

Sharpen&Bend: recovering curved sharp edges in triangle meshes produced by feature-insensitive sampling.

Various acquisition, analysis, visualization, and compression approaches sample surfaces of 3D shapes in a uniform fashion without any attempt to align the samples with sharp edges or to adapt the sampling density to the surface curvature. Consequently, triangle meshes that interpolate these samples usually chamfer sharp features and exhibit a relatively large error in their vicinity. We present two new filters that improve the quality of these resampled models. EdgeSharpener restores the sharp edges by splitting the chamfer edges and forcing the new vertices to lie on intersections of planes extending the smooth surfaces incident upon these chamfers. Bender refines the resulting triangle mesh using an interpolating subdivision scheme that preserves the sharpness of the recovered sharp edges while bending their polyline approximations into smooth curves. A combined Sharpen&Bend postprocessing significantly reduces the error produced by feature-insensitive sampling processes. For example, we have observed that the mean-squared distortion introduced by the SwingWrapper remeshing-based compressor can often be reduced by 80 percent executing EdgeSharpener alone after decompression. For models with curved regions, this error may be further reduced by an additional 60 percent if we follow the EdgeSharpening phase by Bender.