Center for Integrative Biomedical Computing

SCI Publications


M. Datar, I. Lyu, S. Kim, J. Cates, M.A. Styner, R.T. Whitaker. “Geodesic distances to landmarks for dense correspondence on ensembles of complex shapes,” In Proceedings of Medical Image Computing and Computer-Assisted Intervention (MICCAI 2011), Vol. 16(Pt. 2), pp. 19--26. 2013.
PubMed ID: 24579119


Establishing correspondence points across a set of biomedical shapes is an important technology for a variety of applications that rely on statistical analysis of individual subjects and populations. The inherent complexity (e.g. cortical surface shapes) and variability (e.g. cardiac chambers) evident in many biomedical shapes introduce significant challenges in finding a useful set of dense correspondences. Application specific strategies, such as registration of simplified (e.g. inflated or smoothed) surfaces or relying on manually placed landmarks, provide some improvement but suffer from limitations including increased computational complexity and ambiguity in landmark placement. This paper proposes a method for dense point correspondence on shape ensembles using geodesic distances to a priori landmarks as features. A novel set of numerical techniques for fast computation of geodesic distances to point sets is used to extract these features. The proposed method minimizes the ensemble entropy based on these features, resulting in isometry invariant correspondences in a very general, flexible framework.

D.J. Dosdall, R. Ranjan, K. Higuchi, E. Kholmovski, N. Angel, L. Li, R.S. Macleod, L. Norlund, A. Olsen, C.J. Davies, N.F. Marrouche. “Chronic atrial fibrillation causes left ventricular dysfunction in dogs but not goats: experience with dogs, goats, and pigs,” In American Journal of Physiology: Heart and Circulatory Physiology, Vol. 305, No. 5, pp. H725--H731. September, 2013.
DOI: 10.1152/ajpheart.00440.2013
PubMed ID: 23812387
PubMed Central ID: PMC4116536


Structural remodeling in chronic atrial fibrillation (AF) occurs over weeks to months. To study the electrophysiological, structural, and functional changes that occur in chronic AF, the selection of the best animal model is critical. AF was induced by rapid atrial pacing (50-Hz stimulation every other second) in pigs (n = 4), dogs (n = 8), and goats (n = 9). Animals underwent MRIs at baseline and 6 mo to evaluate left ventricular (LV) ejection fraction (EF). Dogs were given metoprolol (50-100 mg po bid) and digoxin (0.0625-0.125 mg po bid) to limit the ventricular response rate to ot appropriate for chronic rapid atrial pacing-induced AF studies. Rate-controlled chronic AF in the dog model developed HF and LV fibrosis, whereas the goat model developed only atrial fibrosis without ventricular dysfunction and fibrosis. Both the dog and goat models are representative of segments of the patient population with chronic AF.

Keywords: animal models, chronic atrial fibrillation, fibrosis, heart failure, rapid atrial pacing

B. Erem, J. Coll-Font, R.M. Orellana, P. Stovicek, D.H. Brooks, R.S. MacLeod. “Noninvasive reconstruction of potentials on endocardial surface from body surface potentials and CT imaging of partial torso,” In Journal of Electrocardiology, Vol. 46, No. 4, pp. e28. 2013.
DOI: 10.1016/j.jelectrocard.2013.05.104

B. Erem, R.M. Orellana, P. Stovicek, D.H. Brooks, R.S. MacLeod. “Improved averaging of multi-lead ECGs and electrograms,” In Journal of Electrocardiology, Vol. 46, No. 4, Elsevier, pp. e28. July, 2013.
DOI: 10.1016/j.jelectrocard.2013.05.103

T. Fogal, A. Schiewe, J. Krüger. “An Analysis of Scalable GPU-Based Ray-Guided Volume Rendering,” In 2013 IEEE Symposium on Large Data Analysis and Visualization (LDAV), 2013.


Volume rendering continues to be a critical method for analyzing large-scale scalar fields, in disciplines as diverse as biomedical engineering and computational fluid dynamics. Commodity desktop hardware has struggled to keep pace with data size increases, challenging modern visualization software to deliver responsive interactions for O(N3) algorithms such as volume rendering. We target the data type common in these domains: regularly-structured data.

In this work, we demonstrate that the major limitation of most volume rendering approaches is their inability to switch the data sampling rate (and thus data size) quickly. Using a volume renderer inspired by recent work, we demonstrate that the actual amount of visualizable data for a scene is typically bound considerably lower than the memory available on a commodity GPU. Our instrumented renderer is used to investigate design decisions typically swept under the rug in volume rendering literature. The renderer is freely available, with binaries for all major platforms as well as full source code, to encourage reproduction and comparison with future research.

G. Gardner, A. Morris, K. Higuchi, R.S. MacLeod, J. Cates. “A Point-Correspondence Approach to Describing the Distribution of Image Features on Anatomical Surfaces, with Application to Atrial Fibrillation,” In Proceedings of the 2013 IEEE 10th International Symposium on Biomedical Imaging (ISBI), pp. 226--229. 2013.
DOI: 10.1109/ISBI.2013.6556453


This paper describes a framework for summarizing and comparing the distributions of image features on anatomical shape surfaces in populations. The approach uses a pointbased correspondence model to establish a mapping among surface positions and may be useful for anatomy that exhibits a relatively high degree of shape variability, such as cardiac anatomy. The approach is motivated by the MRI-based study of diseased, or fibrotic, tissue in the left atrium of atrial fibrillation (AF) patients, which has been difficult to measure quantitatively using more established image and surface registration techniques. The proposed method is to establish a set of point correspondences across a population of shape surfaces that provides a mapping from any surface to a common coordinate frame, where local features like fibrosis can be directly compared. To establish correspondence, we use a previously-described statistical optimization of particle-based shape representations. For our atrial fibrillation population, the proposed method provides evidence that more intense and widely distributed fibrosis patterns exist in patients that do not respond well to radiofrequency ablation therapy.

J. Grüninger, J. Krüger. “The impact of display bezels on stereoscopic vision for tiled displays,” In Proceedings of the 19th ACM Symposium on Virtual Reality Software and Technology (VRST), pp. 241--250. 2013.
DOI: 10.1145/2503713.2503717


In recent years high-resolution tiled display systems have gained significant attention in scientific and information visualization of large-scale data. Modern tiled display setups are based on either video projectors or LCD screens. While LCD screens are the preferred solution for monoscopic setups, stereoscopic displays almost exclusively consist of some kind of video projection. This is because projections can significantly reduce gaps between tiles, while LCD screens require a bezel around the panel. Projection setups, however, suffer from a number of maintenance issues that are avoided by LCD screens. For example, projector alignment is a very time-consuming task that needs to be repeated at intervals, and different aging states of lamps and filters cause color inconsistencies. The growing availability of inexpensive stereoscopic LCDs for television and gaming allows one to build high-resolution stereoscopic tiled display walls with the same dimensions and resolution as projection systems at a fraction of the cost, while avoiding the aforementioned issues. The only drawback is the increased gap size between tiles.

In this paper, we investigate the effects of bezels on the stereo perception with three surveys and show, that smaller LCD bezels and larger displays significantly increase stereo perception on display wall systems. We also show that the bezel color is not very important and that bezels can negatively affect the adaption times to the stereoscopic effect but improve task completion times. Finally, we present guidelines for the setup of tiled stereoscopic display wall systems.

D.K. Hammond, Y. Gur, C.R. Johnson. “Graph Diffusion Distance: A Difference Measure for Weighted Graphs Based on the Graph Laplacian Exponential Kernel,” In Proceedings of the IEEE global conference on information and signal processing (GlobalSIP'13), Austin, Texas, pp. 419--422. 2013.
DOI: 10.1109/GlobalSIP.2013.6736904


We propose a novel difference metric, called the graph diffusion distance (GDD), for quantifying the difference between two weighted graphs with the same number of vertices. Our approach is based on measuring the average similarity of heat diffusion on each graph. We compute the graph Laplacian exponential kernel matrices, corresponding to repeatedly solving the heat diffusion problem with initial conditions localized to single vertices. The GDD is then given by the Frobenius norm of the difference of the kernels, at the diffusion time yielding the maximum difference. We study properties of the proposed distance on both synthetic examples, and on real-data graphs representing human anatomical brain connectivity.

X. Hao, P.T. Fletcher. “Joint Fractional Segmentation and Multi-Tensor Estimation in Diffusion MRI,” In Proceedings of the International Conference on Information Processing in Medical Imaging (IPMI), Lecture Notes in Computer Science (LNCS), pp. (accepted). 2013.


In this paper we present a novel Bayesian approach for fractional segmentation of white matter tracts and simultaneous estimation of a multi-tensor diffusion model. Our model consists of several white matter tracts, each with a corresponding weight and tensor compartment in each voxel. By incorporating a prior that assumes the tensor fields inside each tract are spatially correlated, we are able to reliably estimate multiple tensor compartments in fiber crossing regions, even with low angular diffusion-weighted imaging (DWI). Our model distinguishes the diffusion compartment associated with each tract, which reduces the effects of partial voluming and achieves more reliable statistics of diffusion measurements.We test our method on synthetic data with known ground truth and show that we can recover the correct volume fractions and tensor compartments. We also demonstrate that the proposed method results in improved segmentation and diffusion measurement statistics on real data in the presence of crossing tracts and partial voluming.

M.D. Harris, S.P. Reese, C.L. Peters, J.A. Weiss, A.E. Anderson. “Three-dimensional Quantification of Femoral Head Shape in Controls and Patients with Cam-type Femoroacetabular Impingement,” In Annals of Biomedical Engineering, Vol. 41, No. 6, pp. 1162--1171. 2013.
DOI: 10.1007/s10439-013-0762-1


An objective measurement technique to quantify 3D femoral head shape was developed and applied to normal subjects and patients with cam-type femoroacetabular impingement (FAI). 3D reconstructions were made from high-resolution CT images of 15 cam and 15 control femurs. Femoral heads were fit to ideal geometries consisting of rotational conchoids and spheres. Geometric similarity between native femoral heads and ideal shapes was quantified. The maximum distance native femoral heads protruded above ideal shapes and the protrusion area were measured. Conchoids provided a significantly better fit to native femoral head geometry than spheres for both groups. Cam-type FAI femurs had significantly greater maximum deviations (4.99 ± 0.39 mm and 4.08 ± 0.37 mm) than controls (2.41 ± 0.31 mm and 1.75 ± 0.30 mm) when fit to spheres or conchoids, respectively. The area of native femoral heads protruding above ideal shapes was significantly larger in controls when a lower threshold of 0.1 mm (for spheres) and 0.01 mm (for conchoids) was used to define a protrusion. The 3D measurement technique described herein could supplement measurements of radiographs in the diagnosis of cam-type FAI. Deviations up to 2.5 mm from ideal shapes can be expected in normal femurs while deviations of 4–5 mm are characteristic of cam-type FAI.

M.D. Harris, M. Datar, R.T. Whitaker, E.R. Jurrus, C.L. Peters, A.E. Anderson. “Statistical Shape Modeling of Cam Femoroacetabular Impingement,” In Journal of Orthopaedic Research, Vol. 31, No. 10, pp. 1620--1626. 2013.
DOI: 10.1002/jor.22389


Statistical shape modeling (SSM) was used to quantify 3D variation and morphologic differences between femurs with and without cam femoroacetabular impingement (FAI). 3D surfaces were generated from CT scans of femurs from 41 controls and 30 cam FAI patients. SSM correspondence particles were optimally positioned on each surface using a gradient descent energy function. Mean shapes for groups were defined. Morphological differences between group mean shapes and between the control mean and individual patients were calculated. Principal component analysis described anatomical variation. Among all femurs, the first six modes (or principal components) captured significant variations, which comprised 84% of cumulative variation. The first two modes, which described trochanteric height and femoral neck width, were significantly different between groups. The mean cam femur shape protruded above the control mean by a maximum of 3.3 mm with sustained protrusions of 2.5–3.0 mm along the anterolateral head-neck junction/distal anterior neck. SSM described variations in femoral morphology that corresponded well with areas prone to damage. Shape variation described by the first two modes may facilitate objective characterization of cam FAI deformities; variation beyond may be inherent population variance. SSM could characterize disease severity and guide surgical resection of bone.

H. Hernandez, J. Knezevic, T. Fogal, T. Sherman, T. Jevremovic. “Visual numerical steering in 3D AGENT code system for advanced nuclear reactor modeling and design,” In Annals of Nuclear Energy, Vol. 55, pp. 248--257. 2013.


The AGENT simulation system is used for detailed three-dimensional modeling of neutron transport and corresponding properties of nuclear reactors of any design. Numerical solution to the neutron transport equation in the AGENT system is based on the Method of Characteristics (MOCs) and the theory of R-functions. The latter of which is used for accurately describing current and future heterogeneous lattices of reactor core configurations. The AGENT code has been extensively verified to assure a high degree of accuracy for predicting neutron three-dimensional point-wise flux spatial distributions, power peaking factors, reaction rates, and eigenvalues. In this paper, a new AGENT code feature, a computational steering, is presented. This new feature provides a novel way for using deterministic codes for fast evaluation of reactor core parameters, at no loss to accuracy. The computational steering framework as developed at the Technische Universität München is smoothly integrated into the AGENT solver. This framework allows for an arbitrary interruption of AGENT simulation, allowing the solver to restart with updated parameters. One possible use of this is to accelerate the convergence of the final values resulting in significantly reduced simulation times. Using this computational steering in the AGENT system, coarse MOC resolution parameters can initially be selected and later update them – while the simulation is actively running – into fine resolution parameters. The utility of the steering framework is demonstrated using the geometry of a research reactor at the University of Utah: this new approach provides a savings in CPU time on the order of 50%.

Keywords: Numerical steering, AGENT code, Deterministic neutron transport codes, Method of Characteristics, R-functions, Numerical visualizations

K. Higuchi, M. Akkaya, M. Koopmann, J.J. Blauer, N.S. Burgon, K. Damal, R. Ranjan, E. Kholmovski, R.S. Macleod, N.F. Marrouche.. “The Effect of Fat Pad Modification during Ablation of Atrial Fibrillation: Late Gadolinium Enhancement MRI Analysis,” In Pacing and Clinical Electrophysiology (PACE), Vol. 36, No. 4, pp. 467--476. April, 2013.
DOI: 10.1111/pace.12084
PubMed ID: 23356963
PubMed Central ID: PMC3651513


Background: Magnetic resonance imaging (MRI) can visualize locations of both the ablation scar on the left atrium (LA) after atrial fibrillation (AF) ablation and epicardial fat pads (FPs) containing ganglionated plexi (GP).

Methods: We investigated 60 patients who underwent pulmonary vein antrum (PVA) isolation along with LA posterior wall and septal debulking for AF. FPs around the LA surface in well-known GP areas (which were considered as the substitution of GP areas around the LA) were segmented from the dark-blood MRI. Then the FP and the ablation scar image visualized by late gadolinium enhancement (LGE)-MRI on the LA were merged together. Overlapping areas of FP and the ablation scar image were considered as the ablated FP areas containing GP. Patients underwent 24-hour Holter monitoring after ablation for the analysis of heart rate variability.

Results: Ablated FP area was significantly wider in patients without AF recurrence than those in patients with recurrence (5.6 ± 3.1 cm2 vs 4.2 ± 2.7 cm2 ,P = 0.03). The mean values of both percentage of differences greater than 50 ms in the RR intervals (pRR > 50) and standard deviation of RR intervals over the entire analyzed period (SDNN), which were obtained from 24-hour Holter monitoring 1-day post-AF ablation, were significantly lower in patients without recurrence than those in patients with recurrence (5.8 ± 6.0% vs 14.0 ± 10.1%; P = 0.0005, 78.7 ± 32.4 ms vs 109.2 ± 43.5 ms; P = 0.005). There was a significant negative correlation between SDNN and the percentage of ablated FP area (Y =- 1.3168X + 118.96, R2 = 0.1576, P = 0.003).

Conclusion: Extensively ablating LA covering GP areas along with PVA isolation enhanced the denervation of autonomic nerve system and seemed to improve procedural outcome in patients with AF.

Keywords: ganglionated plexi, fat pad, atrial fibrillation, catheter ablation, LGE-MRI

F. Jiao, J.M. Phillips, Y. Gur, C.R. Johnson. “Uncertainty Visualization in HARDI based on Ensembles of ODFs,” In Proceedings of 2013 IEEE Pacific Visualization Symposium, pp. 193--200. 2013.
PubMed ID: 24466504
PubMed Central ID: PMC3898522


In this paper, we propose a new and accurate technique for uncertainty analysis and uncertainty visualization based on fiber orientation distribution function (ODF) glyphs, associated with high angular resolution diffusion imaging (HARDI). Our visualization applies volume rendering techniques to an ensemble of 3D ODF glyphs, which we call SIP functions of diffusion shapes, to capture their variability due to underlying uncertainty. This rendering elucidates the complex heteroscedastic structural variation in these shapes. Furthermore, we quantify the extent of this variation by measuring the fraction of the volume of these shapes, which is consistent across all noise levels, the certain volume ratio. Our uncertainty analysis and visualization framework is then applied to synthetic data, as well as to HARDI human-brain data, to study the impact of various image acquisition parameters and background noise levels on the diffusion shapes.

C.R. Johnson, A. Pang (Eds.). “International Journal for Uncertainty Quantification,” Subtitled “Special Issue on Working with Uncertainty: Representation, Quantification, Propagation, Visualization, and Communication of Uncertainty,” In Int. J. Uncertainty Quantification, Vol. 3, No. 2, Begell House, Inc., pp. vii--viii. 2013.
ISSN: 2152-5080
DOI: 10.1615/Int.J.UncertaintyQuantification.v3.i2

C.R. Johnson, A. Pang (Eds.). “International Journal for Uncertainty Quantification,” Subtitled “Special Issue on Working with Uncertainty: Representation, Quantification, Propagation, Visualization, and Communication of Uncertainty,” In Int. J. Uncertainty Quantification, Vol. 3, No. 3, Begell House, Inc., 2013.
ISSN: 2152-5080
DOI: 10.1615/Int.J.UncertaintyQuantification.v3.i3

C. Jones, M. Seyedhosseini, M. Ellisman, T. Tasdizen. “Neuron Segmentation in Electron Microscopy Images Using Partial Differential Equations,” In Proceedings of 2013 IEEE 10th International Symposium on Biomedical Imaging (ISBI), pp. 1457--1460. April, 2013.
DOI: 10.1109/ISBI.2013.6556809


In connectomics, neuroscientists seek to identify the synaptic connections between neurons. Segmentation of cell membranes using supervised learning algorithms on electron microscopy images of brain tissue is often done to assist in this effort. Here we present a partial differential equation with a novel growth term to improve the results of a supervised learning algorithm. We also introduce a new method for representing the resulting image that allows for a more dynamic thresholding to further improve the result. Using these two processes we are able to close small to medium sized gaps in the cell membrane detection and improve the Rand error by as much as 9\% over the initial supervised segmentation.

K.B. Jones, M. Datar, S. Ravichandran, H. Jin, E. Jurrus, R.T. Whitaker, M.R. Capecchi. “Toward an Understanding of the Short Bone Phenotype Associated with Multiple Osteochondromas,” In Journal of Orthopaedic Research, Vol. 31, No. 4, pp. 651--657. 2013.
DOI: 10.1002/jor.22280
PubMed ID: 23192691
PubMed Central ID: PMC3683979


Individuals with multiple osteochondromas (MO) demonstrate shortened long bones. Ext1 or Ext2 haploinsufficiency cannot recapitulate the phenotype in mice. Loss of heterozygosity for Ext1 may induce shortening by steal of longitudinal growth into osteochondromas or by a general derangement of physeal signaling. We induced osteochondromagenesis at different time points during skeletal growth in a mouse genetic model, then analyzed femora and tibiae at 12 weeks using micro-CT and a point-distribution-based shape analysis. Bone lengths and volumes were compared. Metaphyseal volume deviations from normal, as a measure of phenotypic widening, were tested for correlation with length deviations. Mice with osteochondromas had shorter femora and tibiae than controls, more consistently when osteochondromagenesis was induced earlier during skeletal growth. Volumetric metaphyseal widening did not correlate with longitudinal shortening, although some of the most severe shortening was in bones with abundant osteochondromas. Loss of heterozygosity for Ext1 was sufficient to drive bone shortening in a mouse model of MO, but shortening did not correlate with osteochondroma volumetric growth. While a steal phenomenon seems apparent in individual cases, some other mechanism must also be capable of contributing to the short bone phenotype, independent of osteochondroma formation. Clones of chondrocytes lacking functional heparan sulfate must blunt physeal signaling generally, rather than stealing growth potential focally. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 651-657, 2013.

K.S. McDowell, F. Vadakkumpadan, R. Blake, J. Blauer, G.t Plank, R.S. MacLeod, N.A. Trayanova. “Mechanistic Inquiry into the Role of Tissue Remodeling in Fibrotic Lesions in Human Atrial Fibrillation,” In Biophysical Journal, Vol. 104, pp. 2764--2773. 2013.
DOI: 10.1016/j.bpj.2013.05.025
PubMed ID: 23790385
PubMed Central ID: PMC3686346


Atrial fibrillation (AF), the most common arrhythmia in humans, is initiated when triggered activity from the pulmonary veins propagates into atrial tissue and degrades into reentrant activity. Although experimental and clinical findings show a correlation between atrial fibrosis and AF, the causal relationship between the two remains elusive. This study used an array of 3D computational models with different representations of fibrosis based on a patient-specific atrial geometry with accurate fibrotic distribution to determine the mechanisms by which fibrosis underlies the degradation of a pulmonary vein ectopic beat into AF. Fibrotic lesions in models were represented with combinations of: gap junction remodeling; collagen deposition; and myofibroblast proliferation with electrotonic or paracrine effects on neighboring myocytes. The study found that the occurrence of gap junction remodeling and the subsequent conduction slowing in the fibrotic lesions was a necessary but not sufficient condition for AF development, whereas myofibroblast proliferation and the subsequent electrophysiological effect on neighboring myocytes within the fibrotic lesions was the sufficient condition necessary for reentry formation. Collagen did not alter the arrhythmogenic outcome resulting from the other fibrosis components. Reentrant circuits formed throughout the noncontiguous fibrotic lesions, without anchoring to a specific fibrotic lesion.

C. McGann, N. Akoum, A. Patel, E. Kholmovski, P. Revelo, K. Damal, B. Wilson, J. Cates, A. Harrison, R. Ranjan, N.S. Burgon, T. Greene, D. Kim, E.V.R. DiBella, D. Parker, R.S. MacLeod, N.F. Marrouche. “Atrial Fibrillation Ablation Outcome is Predicted by Left Atrial Remodeling on MRI,” In Circulation: Arrhythmia and Electrophysiology, Note: Published online before print., December, 2013.
DOI: 10.1161/CIRCEP.113.000689


Background: While catheter ablation therapy for atrial fibrillation (AF) is becoming more common, results vary widely and patient selection criteria remain poorly defined. We hypothesized that late gadolinium enhancement magnetic resonance imaging (LGE-MRI) can identify left atrial (LA) wall structural remodeling (SRM) and stratify patients who are likely or not to benefit from ablation therapy.

Methods and Results: LGE-MRI was performed on 426 consecutive AF patients without contraindications to MRI and before undergoing their first ablation procedure and on 21 non-AF control subjects. Patients were categorized by SRM stage (I-IV) based on percentage of LA wall enhancement for correlation with procedure outcomes. Histological validation of SRM was performed comparing LGE-MRI to surgical biopsy. A total of 386 patients (91%) with adequate LGE-MRI scans were included in the study. Post-ablation, 123 (31.9%) experienced recurrent atrial arrhythmias over one-year follow-up. Recurrent arrhythmias (failed ablations) occurred at higher SRM stages with 28/133 (21.0%) stage I, 40/140 (29.3%) stage II, 24/71 (33.8%) stage III, and 30/42 (71.4%) stage IV. In multi-variate analysis, ablation outcome was best predicted by advanced SRM stage (hazard ratio (HR) 4.89; p

Keywords: atrial fibrillation arrhythmia, catheter ablation, magnetic resonance imaging, remodeling, outcome