K.S. McDowell, F. Vadakkumpadan, R. Blake, J. Blauer, G. Plank, R.S. MacLeod, N.A. Trayanova.
Methodology for patient-specific modeling of atrial fibrosis as a substrate for atrial fibrillation, In Journal of Electrocardiology, Vol. 45, No. 6, pp. 640--645. 2012.
PubMed ID: 22999492
PubMed Central ID: PMC3515859
Personalized computational cardiac models are emerging as an important tool for studying cardiac arrhythmia mechanisms, and have the potential to become powerful instruments for guiding clinical anti-arrhythmia therapy. In this article, we present the methodology for constructing a patient-specific model of atrial fibrosis as a substrate for atrial fibrillation. The model is constructed from high-resolution late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) images acquired in vivo from a patient suffering from persistent atrial fibrillation, accurately capturing both the patient's atrial geometry and the distribution of the fibrotic regions in the atria. Atrial fiber orientation is estimated using a novel image-based method, and fibrosis is represented in the patient-specific fibrotic regions as incorporating collagenous septa, gap junction remodeling, and myofibroblast proliferation. A proof-of-concept simulation result of reentrant circuits underlying atrial fibrillation in the model of the patient's fibrotic atrium is presented to demonstrate the completion of methodology development.
Keywords: Patient-specific modeling, Computational model, Atrial fibrillation, Atrial fibrosis
Q. Meng, J. Hall, H. Rutigliano, X. Zhou, B.R. Sessions, R. Stott, K. Panter, C.J. Davies, R. Ranjan, D. Dosdall, R.S. MacLeod, N. Marrouche, K.L. White, Z. Wang, I.A. Polejaeva.
30 Generation of Cloned Transgenic Goats with Cardiac Specific Overexpression of Transforming Growth Factor β1, In Reproduction, Fertility and Development, Vol. 25, No. 1, pp. 162--163. 2012.
Transforming growth factor β1 (TGF-β1) has a potent profibrotic function and is central to signaling cascades involved in interstitial fibrosis, which plays a critical role in the pathobiology of cardiomyopathy and contributes to diastolic and systolic dysfunction. In addition, fibrotic remodeling is responsible for generation of re-entry circuits that promote arrhythmias (Bujak and Frangogiannis 2007 Cardiovasc. Res. 74, 184–195). Due to the small size of the heart, functional electrophysiology of transgenic mice is problematic. Large transgenic animal models have the potential to offer insights into conduction heterogeneity associated with fibrosis and the role of fibrosis in cardiovascular diseases. The goal of this study was to generate transgenic goats overexpressing an active form of TGFβ-1 under control of the cardiac-specific α-myosin heavy chain promoter (α-MHC). A pcDNA3.1DV5-MHC-TGF-β1cys33ser vector was constructed by subcloning the MHC-TGF-β1 fragment from the plasmid pUC-BM20-MHC-TGF-β1 (Nakajima et al. 2000 Circ. Res. 86, 571–579) into the pcDNA3.1D V5 vector. The Neon transfection system was used to electroporate primary goat fetal fibroblasts. After G418 selection and PCR screening, transgenic cells were used for SCNT. Oocytes were collected by slicing ovaries from an abattoir and matured in vitro in an incubator with 5\% CO2 in air. Cumulus cells were removed at 21 to 23 h post-maturation. Oocytes were enucleated by aspirating the first polar body and nearby cytoplasm by micromanipulation in Hepes-buffered SOF medium with 10 µg of cytochalasin B mL–1. Transgenic somatic cells were individually inserted into the perivitelline space and fused with enucleated oocytes using double electrical pulses of 1.8 kV cm–1 (40 µs each). Reconstructed embryos were activated by ionomycin (5 min) and DMAP and cycloheximide (CHX) treatments. Cloned embryos were cultured in G1 medium for 12 to 60 h in vitro and then transferred into synchronized recipient females. Pregnancy was examined by ultrasonography on day 30 post-transfer. A total of 246 cloned embryos were transferred into 14 recipients that resulted in production of 7 kids. The pregnancy rate was higher in the group cultured for 12 h compared with those cultured 36 to 60 h [44.4\% (n = 9) v. 20\% (n = 5)]. The kidding rates per embryo transferred of these 2 groups were 3.8\% (n = 156) and 1.1\% (n = 90), respectively. The PCR results confirmed that all the clones were transgenic. Phenotype characterization [e.g. gene expression, electrocardiogram (ECG), and magnetic resonance imaging (MRI)] is underway. We demonstrated successful production of transgenic goat via SCNT. To our knowledge, this is the first transgenic goat model produced for cardiovascular research.
B. Paniagua, L. Bompard, J. Cates, R.T. Whitaker, M. Datar, C. Vachet, M. Styner.
Combined SPHARM-PDM and entropy-based particle systems shape analysis framework, In Medical Imaging 2012: Biomedical Applications in Molecular, Structural, and Functional Imaging, SPIE Intl Soc Optical Eng, March, 2012.
PubMed ID: 24027625
PubMed Central ID: PMC3766973
Description of purpose: The NA-MIC SPHARM-PDM Toolbox represents an automated set of tools for the computation of 3D structural statistical shape analysis. SPHARM-PDM solves the correspondence problem by defining a first order ellipsoid aligned, uniform spherical parameterization for each object with correspondence established at equivalently parameterized points. However, SPHARM correspondence has shown to be inadequate for some biological shapes that are not well described by a uniform spherical parameterization. Entropy-based particle systems compute correspondence by representing surfaces as discrete point sets that does not rely on any inherent parameterization. However, they are sensitive to initialization and have little ability to recover from initial errors. By combining both methodologies we compute reliable correspondences in topologically challenging biological shapes. Data: Diverse subcortical structures cohorts were used, obtained from MR brain images. Method(s): The SPHARM-PDM shape analysis toolbox was used to compute point based correspondent models that were then used as initializing particles for the entropy-based particle systems. The combined framework was implemented as a stand-alone Slicer3 module, which works as an end-to-end shape analysis module. Results: The combined SPHARM-PDM-Particle framework has demonstrated to improve correspondence in the example dataset over the conventional SPHARM-PDM toolbox. Conclusions: The work presented in this paper demonstrates a two-sided improvement for the scientific community, being able to 1) find good correspondences among spherically topological shapes, that can be used in many morphometry studies 2) offer an end-to-end solution that will facilitate the access to shape analysis framework to users without computer expertise.
D. Perry, A. Morris, N. Burgon, C. McGann, R.S. MacLeod, J. Cates.
Automatic classification of scar tissue in late gadolinium enhancement cardiac MRI for the assessment of left-atrial wall injury after radiofrequency ablation, In SPIE Proceedings, Vol. 8315, pp. (published online). 2012.
PubMed ID: 24236224
PubMed Central ID: PMC3824273
Radiofrequency ablation is a promising procedure for treating atrial fibrillation (AF) that relies on accurate lesion delivery in the left atrial (LA) wall for success. Late Gadolinium Enhancement MRI (LGE MRI) at three months post-ablation has proven effective for noninvasive assessment of the location and extent of scar formation, which are important factors for predicting patient outcome and planning of redo ablation procedures. We have developed an algorithm for automatic classification in LGE MRI of scar tissue in the LA wall and have evaluated accuracy and consistency compared to manual scar classifications by expert observers. Our approach clusters voxels based on normalized intensity and was chosen through a systematic comparison of the performance of multivariate clustering on many combinations of image texture. Algorithm performance was determined by overlap with ground truth, using multiple overlap measures, and the accuracy of the estimation of the total amount of scar in the LA. Ground truth was determined using the STAPLE algorithm, which produces a probabilistic estimate of the true scar classification from multiple expert manual segmentations. Evaluation of the ground truth data set was based on both inter- and intra-observer agreement, with variation among expert classifiers indicating the difficulty of scar classification for a given a dataset. Our proposed automatic scar classification algorithm performs well for both scar localization and estimation of scar volume: for ground truth datasets considered easy, variability from the ground truth was low; for those considered difficult, variability from ground truth was on par with the variability across experts.
K. Potter, R.M. Kirby, D. Xiu, C.R. Johnson.
Interactive visualization of probability and cumulative density functions, In International Journal of Uncertainty Quantification, Vol. 2, No. 4, pp. 397--412. 2012.
PubMed ID: 23543120
PubMed Central ID: PMC3609671
The probability density function (PDF), and its corresponding cumulative density function (CDF), provide direct statistical insight into the characterization of a random process or field. Typically displayed as a histogram, one can infer probabilities of the occurrence of particular events. When examining a field over some two-dimensional domain in which at each point a PDF of the function values is available, it is challenging to assess the global (stochastic) features present within the field. In this paper, we present a visualization system that allows the user to examine two-dimensional data sets in which PDF (or CDF) information is available at any position within the domain. The tool provides a contour display showing the normed difference between the PDFs and an ansatz PDF selected by the user, and furthermore allows the user to interactively examine the PDF at any particular position. Canonical examples of the tool are provided to help guide the reader into the mapping of stochastic information to visual cues along with a description of the use of the tool for examining data generated from a uncertainty quantification exercise accomplished within the field of electrophysiology.
Keywords: visualization, probability density function, cumulative density function, generalized polynomial chaos, stochastic Galerkin methods, stochastic collocation methods
K. Potter, P. Rosen, C.R. Johnson.
From Quantification to Visualization: A Taxonomy of Uncertainty Visualization Approaches, In Uncertainty Quantification in Scientific Computing, IFIP Advances in Information and Communication Technology Series, Vol. 377, Edited by Andrew Dienstfrey and Ronald Boisvert, Springer, pp. 226--249. 2012.
Quantifying uncertainty is an increasingly important topic across many domains. The uncertainties present in data come with many diverse representations having originated from a wide variety of domains. Communicating these uncertainties is a task often left to visualization without clear connection between the quantification and visualization. In this paper, we first identify frequently occurring types of uncertainty. Second, we connect those uncertainty representations to ones commonly used in visualization. We then look at various approaches to visualizing this uncertainty by partitioning the work based on the dimensionality of the data and the dimensionality of the uncertainty. We also discuss noteworthy exceptions to our taxonomy along with future research directions for the uncertainty visualization community.
Keywords: scidac, netl, uncertainty visualization
M.W. Prastawa, S.P. Awate, G. Gerig.
Building Spatiotemporal Anatomical Models using Joint 4-D Segmentation, Registration, and Subject-Speci fic Atlas Estimation, In Proceedings of the 2012 IEEE Mathematical Methods in Biomedical Image Analysis (MMBIA) Conference, pp. 49--56. 2012.
PubMed ID: 23568185
PubMed Central ID: PMC3615562
Longitudinal analysis of anatomical changes is a vital component in many personalized-medicine applications for predicting disease onset, determining growth/atrophy patterns, evaluating disease progression, and monitoring recovery. Estimating anatomical changes in longitudinal studies, especially through magnetic resonance (MR) images, is challenging because of temporal variability in shape (e.g. from growth/atrophy) and appearance (e.g. due to imaging parameters and tissue properties affecting intensity contrast, or from scanner calibration). This paper proposes a novel mathematical framework for constructing subject-specific longitudinal anatomical models. The proposed method solves a generalized problem of joint segmentation, registration, and subject-specific atlas building, which involves not just two images, but an entire longitudinal image sequence. The proposed framework describes a novel approach that integrates fundamental principles that underpin methods for image segmentation, image registration, and atlas construction. This paper presents evaluation on simulated longitudinal data and on clinical longitudinal brain MRI data. The results demonstrate that the proposed framework effectively integrates information from 4-D spatiotemporal data to generate spatiotemporal models that allow analysis of anatomical changes over time.
Keywords: namic, adni, autism
R. Ranjan, E.G. Kholmovski, J. Blauer, S. Vijayakumar, N.A. Volland, M.E. Salama, D.L. Parker, R.S. MacLeod, N.F. Marrouche.
Identification and Acute Targeting of Gaps in Atrial Ablation Lesion Sets Using a Real-Time Magnetic Resonance Imaging System, In Circulation: Arrhythmia and Electrophysiology, Vol. 5, pp. 1130--1135. 2012.
PubMed ID: 23071143
PubMed Central ID: PMC3691079
Background - Radiofrequency ablation is routinely used to treat cardiac arrhythmias, but gaps remain in ablation lesion sets because there is no direct visualization of ablation-related changes. In this study, we acutely identify and target gaps using a real-time magnetic resonance imaging (RT-MRI) system, leading to a complete and transmural ablation in the atrium.
Methods and Results - A swine model was used for these studies (n=12). Ablation lesions with a gap were created in the atrium using fluoroscopy and an electroanatomic system in the first group (n=5). The animal was then moved to a 3-tesla MRI system where high-resolution late gadolinium enhancement MRI was used to identify the gap. Using an RT-MRI catheter navigation and visualization system, the gap area was ablated in the MR scanner. In a second group (n=7), ablation lesions with varying gaps in between were created under RT-MRI guidance, and gap lengths determined using late gadolinium enhancement MR images were correlated with gap length measured from gross pathology. Gaps up to 1.0 mm were identified using gross pathology, and gaps up to 1.4 mm were identified using late gadolinium enhancement MRI. Using an RT-MRI system with active catheter navigation gaps can be targeted acutely, leading to lesion sets with no gaps. The correlation coefficient (R2) between the gap length was identified using MRI, and the gross pathology was 0.95.
Conclusions - RT-MRI system can be used to identify and acutely target gaps in atrial ablation lesion sets. Acute targeting of gaps in ablation lesion sets can potentially lead to significant improvement in clinical outcomes.
P. Rosen, V. Popescu.
Simplification of Node Position Data for Interactive Visualization of Dynamic Datasets, In IEEE Transactions on Visualization and Computer Graphics (IEEE Visweek 2012 TVCG Track), pp. 1537--1548. 2012.
PubMed ID: 22025753
PubMed Central ID: PMC3411892
We propose to aid the interactive visualization of time-varying spatial datasets by simplifying node position data over the entire simulation as opposed to over individual states. Our approach is based on two observations. The first observation is that the trajectory of some nodes can be approximated well without recording the position of the node for every state. The second observation is that there are groups of nodes whose motion from one state to the next can be approximated well with a single transformation. We present dataset simplification techniques that take advantage of this node data redundancy. Our techniques are general, supporting many types of simulations, they achieve good compression factors, and they allow rigorous control of the maximum node position approximation error. We demonstrate our approach in the context of finite element analysis data, of liquid flow simulation data, and of fusion simulation data.
Rectilinear Texture Warping for Fast Adaptive Shadow Mapping, In Proceedings of the ACM SIGGRAPH Symposium on Interactive 3D Graphics and Games (I3D '12), pp. 151--158. 2012.
Conventional shadow mapping relies on uniform sampling for producing hard shadow in an efficient manner. This approach trades image quality in favor of efficiency. A number of approaches improve upon shadow mapping by combining multiple shadow maps or using complex data structures to produce shadow maps with multiple resolutions. By sacrificing some performance, these adaptive methods produce shadows that closely match ground truth.
This paper introduces Rectilinear Texture Warping (RTW) for efficiently generating adaptive shadow maps. RTW images combine the advantages of conventional shadow mapping - a single shadow map, quick construction, and constant time pixel shadow tests, with the primary advantage of adaptive techniques - shadow map resolutions which more closely match those requested by output images. RTW images consist of a conventional texture paired with two 1-D warping maps that form a rectilinear grid defining the variation in sampling rate. The quality of shadows produced with RTW shadow maps of standard resolutions, i.e. 2,048×2,048 texture for 1080p output images, approaches that of raytraced results while low overhead permits rendering at hundreds of frames per second.
Keywords: Rendering, Shadow Algorithms, Adaptive Sampling
L. Zhu, Y. Gao, A. Yezzi, R.S. MacLeod, J. Cates, A. Tannenbaum.
Automatic Segmentation of the Left Atrium from MRI Images using Salient Feature and Contour Evolution, In Proceedings of the 34th Annual International Conference of the IEEE EMBS, pp. 3211--214. 2012.
PubMed ID: 23366609
PubMed Central ID: PMC3652873
We propose an automatic approach for segmenting the left atrium from MRI images. In particular, the thoracic aorta is detected and used as a salient feature to find a seed region that lies inside the left atrium. A hybrid energy that combines robust statistics and localized region intensity information is employed to evolve active contours from the seed region to capture the whole left atrium. The experimental results demonstrate the accuracy and robustness of our approach.
N. Akoum, M. Daccarett, C. McGann, N. Segerson, G. Vergara, S. Kuppahally, T. Badger, N. Burgon, T. Haslam, E. Kholmovski, R.S. MacLeod, N.F. Marrouche.
Atrial fibrosis helps select the appropriate patient and strategy in catheter ablation of atrial fibrillation: a DE-MRI guided approach, In Journal of Cardiovascular Electrophysiology, Vol. 22, No. 1, pp. 16--22. 2011.
PubMed ID: 20807271
Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in adult cardiology.1,2 Several studies have demonstrated that AF is associated with electrical, contractile, and structural remodeling (SRM) in the left atrium (LA) that contributes to the persistence and sustainability of the arrhythmia.3-7 It has also been shown that the end result of this remodeling process is loss of atrial myocytes and increased collagen content and hence fibrosis of the LA wall.5 Delayed enhancement MRI (DE-MRI) using gadolinium contrast has been demonstrated to localize and quantify the degree of SRM or fibrosis associated with AF in the LA.8
DE-MRI has also been shown to be useful in localizing and quantifying scar formation in the LA following radiofrequency ablation (RFA).9,10 The pulmonary vein (PV) antral region can be visualized to assess circumferential PV scarring that results from RFA lesions/ablation. In addition, the amount of scarring to the LA after catheter ablation can be quantified as a proportion of the total left atrial volume.
Rhythm control of AF using catheter ablation has yielded varying results in different patient populations.11 Identifying the ideal candidate for catheter ablation remains a significant challenge. In addition, a number of different approaches to catheter ablation have been reported and most experts agree that 1 ablation strategy does not fit allAF patients.11-15 Therefore, selecting the proper strategy for a particular patient is also an important determinant of procedure success.
We used DE-MRI to quantify both the degree of SRM/fibrosis pre-ablation and scar formation post ablation. Our aim was to identify predictors of successful ablation in a group of patients stratified according to pre-ablation fibrosis. This would help select the most appropriate ablation strategy for the individual AF ablation candidate.
N. Andrysco, P. Rosen, V. Popescu, B. Benes, K.R. Gurney.
Experiences in Disseminating Educational Visualizations, In Lecture Notes in Computer Science (7th International Symposium on Visual Computing), Vol. 2, pp. 239--248. September, 2011.
Most visualizations produced in academia or industry have a specific niche audience that is well versed in either the often complicated visualization methods or the scientific domain of the data. Sometimes it is useful to produce visualizations that can communicate results to a broad audience that will not have the domain specific knowledge often needed to understand the results. In this work, we present our experiences in disseminating the results of two studies to national audience. The resulting visualizations and press releases allowed the studies’ researchers to educate a national, if not global, audience.
B.M. Burton, J.D. Tate, B. Erem, D.J. Swenson, D.F. Wang, D.H. Brooks, P.M. van Dam, R.S. MacLeod.
A Toolkit for Forward/Inverse Problems in Electrocardiography within the SCIRun Problem Solving Environment, In Proceedings of the 2011 IEEE Int. Conf. Engineering and Biology Society (EMBC), pp. 267--270. 2011.
PubMed ID: 22254301
PubMed Central ID: PMC3337752
Computational modeling in electrocardiography often requires the examination of cardiac forward and inverse problems in order to non-invasively analyze physiological events that are otherwise inaccessible or unethical to explore. The study of these models can be performed in the open-source SCIRun problem solving environment developed at the Center for Integrative Biomedical Computing (CIBC). A new toolkit within SCIRun provides researchers with essential frameworks for constructing and manipulating electrocardiographic forward and inverse models in a highly efficient and interactive way. The toolkit contains sample networks, tutorials and documentation which direct users through SCIRun-specific approaches in the assembly and execution of these specific problems.
A.N.M. Imroz Choudhury, P. Rosen.
Abstract Visualization of Runtime Memory Behavior, In 6th IEEE International Workshop on Visualizing Software for Understanding and Analysis (VISSOFT 2011), pp. 22--29. 2011.
We present a system for visualizing memory reference traces, the records of the memory transactions performed by a program at runtime. The visualization consists of a structured layout representing the levels of a cache and a set of data glyphs representing the pieces of data in memory being operated on during application runtime. The data glyphs move in response to events generated by a cache simulator, indicating their changing residency in the various levels of the memory hierarchy. Within the levels, the glyphs arrange themselves into higher-order shapes representing the structure of the cache levels, including the composition of their associative cache sets and eviction ordering. We make careful use of different visual channels, including structure, motion, color, and size, to convey salient events as they occur. Our abstract visualization provides a high-level, global view of memory behavior, while giving insight about important events that may help students or software engineers to better understand their software’s performance and behavior.
M. Daccarett, T.J. Badger, N. Akoum, N.S. Burgon, C. Mahnkopf, G.R. Vergara, E.G. Kholmovski, C.J. McGann, D.L. Parker, J. Brachmann, R.S. Macleod, N.F. Marrouche.
Association of left atrial fibrosis detected by delayed-enhancement magnetic resonance imaging and the risk of stroke in patients with atrial fibrillation, In Journal of the American College of Cardiology, Vol. 57, No. 7, pp. 831--838. 2011.
PubMed ID: 21310320
M. Daccarett, C.J. McGann, N.W. Akoum, R.S. MacLeod, N.F. Marrouche.
MRI of the left atrium: predicting clinical outcomes in patients with atrial fibrillation, In Expert Review of Cardiovascular Therapy, Vol. 9, No. 1, pp. 105--111. 2011.
PubMed ID: 21166532
M. Datar, Y. Gur, B. Paniagua, M. Styner, R.T. Whitaker.
Geometric Correspondence for Ensembles of Nonregular Shapes, In Proceedings of Medical Image Computing and Computer-Assisted Intervention (MICCAI 2011), Lecture Notes in Computer Science (LNCS), Vol. 6892, pp. 368--375. 2011.
PubMed ID: 21995050
PubMed Central ID: PMC3346950
An ensemble of biological shapes can be represented and analyzed with a dense set of point correspondences. In previous work, optimal point placement was determined by optimizing an information theoretic criterion that depends on relative spatial locations on different shapes combined with pairwise Euclidean distances between nearby points on the same shape. These choices have prevented such methods from effectively characterizing shapes with complex geometry such as thin or highly curved features. This paper extends previous methods for automatic shape correspondence by taking into account the underlying geometry of individual shapes. This is done by replacing the Euclidean distance for intrashape pairwise particle interactions by the geodesic distance. A novel set of numerical techniques for fast distance computations on curved surfaces is used to extract these distances. In addition, we introduce an intershape penalty term that incorporates surface normal information to achieve better particle correspondences near sharp features. Finally, we demonstrate this new method on synthetic and biological datasets.
B. Erem, D.H. Brooks, P.M. van Dam, J.G. Stinstra, R.S. MacLeod.
Spatiotemporal Estimation of Activation Times of Fractionated ECGs on Complex Heart Surfaces, In Proceedings of the International Coference of the IEEE Engineering in Medicine and Biology Society (EMBS), pp. 5884--5887. 2011.
PubMed ID: 22255678
PubMed Central ID: PMC3345888
Identification of electrical activation or depolarization times on sparsely-sampled complex heart surfaces is of importance to clinicians and researchers in cardiac electrophysiology. We introduce a spatiotemporal approach for activation time estimation which combines prior results using spatial and temporal methods with our own progress on gradient estimation on triangulated surfaces. Results of the method applied to simulated and canine heart data suggest that improvements are possible using this novel combined approach.
B. Erem, P.M. van Dam, D.H. Brooks.
Analysis of the Criteria of Activation-Based Inverse Electrocardiography using Convex Optimization, In Conf Proc IEEE Eng Med Biol Soc, pp. 3913–3916. 2011.
PubMed ID: 22255195
PubMed Central ID: PMC3359386
In inverse electrocardiography (ECG), the problem of finding activation times on the heart noninvasively from body surface potentials is typically formulated as a nonlinear least squares optimization problem. Current solutions rely on iterative algorithms which are sensitive to the presence of local minima. As a result, improved initialization approaches for this problem have been of considerable interest. However, in experiments conducted on a subject with Wolff-Parkinson-White syndrome, we have observed that there may be a mismatch between favorable solutions of the optimization problem and solutions with the desired physiological characteristics. In this work, we use a method based on a convex optimization framework to explore the solution space and analyze whether the optimization criteria target their intended objective.