The NIH/NIGMS
Center for Integrative Biomedical Computing

SCI Publications

2015


K. Gillette, J.D. Tate, B. Kindall, P. Van Dam, E. Kholmovski, R.S. MacLeod. “Generation of Combined-Modality Tetrahedral Meshes,” In Computing in Cardiology, 2015.

ABSTRACT

Registering and combining anatomical components from different image modalities, like MRI and CT that have different tissue contrast, could result in patient-specific models that more closely represent underlying anatomical structures.

In this study, we combined a pair of CT and MRI scans of a pig thorax to make a tetrahedral mesh and compared different registration techniques including rigid, affine, thin plate spline morphing (TPSM), and iterative closest point (ICP), to  superimpose the segmented bones from the CT scan on the soft tissues segmented from the MRI. The TPSM and affine-registered bones remained close to, but not overlapping, important soft tissue.

Simulation models, including an ECG forward model and a defibrillation model, were computed on generated multi-modality meshes after TPSM and affine registration and compared to those based on the original torso mesh.



CIBC. Note: ImageVis3D: An interactive visualization software system for large-scale volume data. Scientific Computing and Imaging Institute (SCI), Download from: http://www.imagevis3d.org, 2015.



C.R. Johnson. “Computational Methods and Software for Bioelectric Field Problems,” In Biomedical Engineering Handbook, 4, Vol. 1, Ch. 43, Edited by J.D. Bronzino and D.R. Peterson, CRC Press, pp. 1--28. 2015.

ABSTRACT

Computer modeling and simulation continue to become more important in the field of bioengineering. The reasons for this growing importance are manyfold. First, mathematical modeling has been shown to be a substantial tool for the investigation of complex biophysical phenomena. Second, since the level of complexity one can model parallels the existing hardware configurations, advances in computer architecture have made it feasible to apply the computational paradigm to complex biophysical systems. Hence, while biological complexity continues to outstrip the capabilities of even the largest computational systems, the computational methodology has taken hold in bioengineering and has been used successfully to suggest physiologically and clinically important scenarios and results.

This chapter provides an overview of numerical techniques that can be applied to a class of bioelectric field problems. Bioelectric field problems are found in a wide variety of biomedical applications, which range from single cells, to organs, up to models that incorporate partial to full human structures. We describe some general modeling techniques that will be applicable, in part, to all the aforementioned applications. We focus our study on a class of bioelectric volume conductor problems that arise in electrocardiography (ECG) and electroencephalography (EEG).

We begin by stating the mathematical formulation for a bioelectric volume conductor, continue by describing the model construction process, and follow with sections on numerical solutions and computational considerations. We continue with a section on error analysis coupled with a brief introduction to adaptive methods. We conclude with a section on software.



C.R. Johnson. “Visualization,” In Encyclopedia of Applied and Computational Mathematics, Edited by Björn Engquist, Springer, pp. 1537-1546. 2015.
ISBN: 978-3-540-70528-4
DOI: 10.1007/978-3-540-70529-1_368



CIBC. Note: map3d: Interactive scientific visualization tool for bioengineering data. Scientific Computing and Imaging Institute (SCI), Download from: http://www.sci.utah.edu/cibc/software.html, 2015.



K.S. McDowell, S. Zahid, F. Vadakkumpadan, J.J. Blauer, R.S. MacLeod, N.A. Trayanova. “Virtual Electrophysiological Study of Atrial Fibrillation in Fibrotic Remodeling,” In PLoS ONE, Vol. 10, No. 2, pp. e0117110. February, 2015.
DOI: 10.1371/journal.pone.0117110

ABSTRACT

Research has indicated that atrial fibrillation (AF) ablation failure is related to the presence of atrial fibrosis. However it remains unclear whether this information can be successfully used in predicting the optimal ablation targets for AF termination. We aimed to provide a proof-of-concept that patient-specific virtual electrophysiological study that combines i) atrial structure and fibrosis distribution from clinical MRI and ii) modeling of atrial electrophysiology, could be used to predict: (1) how fibrosis distribution determines the locations from which paced beats degrade into AF; (2) the dynamic behavior of persistent AF rotors; and (3) the optimal ablation targets in each patient. Four MRI-based patient-specific models of fibrotic left atria were generated, ranging in fibrosis amount. Virtual electrophysiological studies were performed in these models, and where AF was inducible, the dynamics of AF were used to determine the ablation locations that render AF non-inducible. In 2 of the 4 models patient-specific models AF was induced; in these models the distance between a given pacing location and the closest fibrotic region determined whether AF was inducible from that particular location, with only the mid-range distances resulting in arrhythmia. Phase singularities of persistent rotors were found to move within restricted regions of tissue, which were independent of the pacing location from which AF was induced. Electrophysiological sensitivity analysis demonstrated that these regions changed little with variations in electrophysiological parameters. Patient-specific distribution of fibrosis was thus found to be a critical component of AF initiation and maintenance. When the restricted regions encompassing the meander of the persistent phase singularities were modeled as ablation lesions, AF could no longer be induced. The study demonstrates that a patient-specific modeling approach to identify non-invasively AF ablation targets prior to the clinical procedure is feasible.



I. OguzI, J. Cates, M. Datar, B. Paniagua, T. Fletcher, C. Vachet, M. Styner, R. Whitaker. “Entropy-based particle correspondence for shape populations,” In International Journal of Computer Assisted Radiology and Surgery, Springer, pp. 1-12. December, 2015.

ABSTRACT

Purpose
Statistical shape analysis of anatomical structures plays an important role in many medical image analysis applications such as understanding the structural changes in anatomy in various stages of growth or disease. Establishing accurate correspondence across object populations is essential for such statistical shape analysis studies.

Methods
In this paper, we present an entropy-based correspondence framework for computing point-based correspondence among populations of surfaces in a groupwise manner. This robust framework is parameterization-free and computationally efficient. We review the core principles of this method as well as various extensions to deal effectively with surfaces of complex geometry and application-driven correspondence metrics.

Results
We apply our method to synthetic and biological datasets to illustrate the concepts proposed and compare the performance of our framework to existing techniques.

Conclusions
Through the numerous extensions and variations presented here, we create a very flexible framework that can effectively handle objects of various topologies, multi-object complexes, open surfaces, and objects of complex geometry such as high-curvature regions or extremely thin features.



B.R. Parmar, T.R. Jarrett, E.G. Kholmovski, N. Hu, D. Parker, R.S. MacLeod, N.F. Marrouche, R. Ranjan. “Poor scar formation after ablation is associated with atrial fibrillation recurrence,” In Journal of Interventional Cardiac Electrophysiology, Vol. 44, No. 3, pp. 247-256. December, 2015.

ABSTRACT

Purpose
Patients routinely undergo ablation for atrial fibrillation (AF) but the recurrence rate remains high. We explored in this study whether poor scar formation as seen on late-gadolinium enhancement magnetic resonance imaging (LGE-MRI) correlates with AF recurrence following ablation.

Methods
We retrospectively identified 94 consecutive patients who underwent their initial ablation for AF at our institution and had pre-procedural magnetic resonance angiography (MRA) merged with left atrial (LA) anatomy in an electroanatomic mapping (EAM) system, ablated areas marked intraprocedurally in EAM, 3-month post-ablation LGE-MRI for assessment of scar, and minimum of 3-months of clinical follow-up. Ablated area was quantified retrospectively in EAM and scarred area was quantified in the 3-month post-ablation LGE-MRI.

Results
With the mean follow-up of 336 days, 26 out of 94 patients had AF recurrence. Age, hypertension, and heart failure were not associated with AF recurrence, but LA size and difference between EAM ablated area and LGE-MRI scar area was associated with higher AF recurrence. For each percent higher difference between EAM ablated area and LGE-MRI scar area, there was a 7–9 % higher AF recurrence (p values 0.001–0.003) depending on the multivariate analysis.

Conclusions
In AF ablation, poor scar formation as seen on LGE-MRI was associated with AF recurrence. Improved mapping and ablation techniques are necessary to achieve the desired LA scar and reduce AF recurrence.



SCI Institute. Note: SCIRun: A Scientific Computing Problem Solving Environment, Scientific Computing and Imaging Institute (SCI), Download from: http://www.scirun.org, 2015.



CIBC. Note: Seg3D: Volumetric Image Segmentation and Visualization. Scientific Computing and Imaging Institute (SCI), Download from: http://www.seg3d.org, 2015.


2014


J.J.E. Blauer, D. Swenson, K. Higuchi, G. Plank, R. Ranjan, N. Marrouche,, R.S. MacLeod. “Sensitivity and Specificity of Substrate Mapping: An In Silico Framework for the Evaluation of Electroanatomical Substrate Mapping Strategies,” In Journal of Cardiovascular Electrophysiology, In Journal of Cardiovascular Electrophysiology, Vol. 25, No. 7, Note: Featured on journal cover., pp. 774--780. May, 2014.

ABSTRACT

Background - Voltage mapping is an important tool for characterizing proarrhythmic electrophysiological substrate, yet it is subject to geometric factors that influence bipolar amplitudes and thus compromise performance. The aim of this study was to characterize the impact of catheter orientation on the ability of bipolar amplitudes to accurately discriminate between healthy and diseased tissues.

Methods and Results - We constructed a three-dimensional, in-silico, bidomain model of cardiac tissue containing transmural lesions of varying diameter. A planar excitation wave was stimulated and electrograms were sampled with a realistic catheter model at multiple positions and orientations. We carried out validation studies in animal experiments of acute ablation lesions mapped with a clinical mapping system. Bipolar electrograms sampled at higher inclination angles of the catheter with respect to the tissue demonstrated improvements in both sensitivity and specificity of lesion detection. Removing low voltage electrograms with concurrent activation of both electrodes, suggesting false attenuation of the bipolar electrogram due to alignment with the excitation wavefront, had little effect on the accuracy of voltage mapping.

Conclusions - Our results demonstrate possible mechanisms for the impact of catheter orientation on voltage mapping accuracy. Moreover, results from our simulations suggest that mapping accuracy may be improved by selectively controlling the inclination of the catheter to record at higher angles with respect to the tissue.

Keywords: arrhythmia, computer-based model, electroanatomical mapping, voltage mapping, bipolar electrogram



J. Bronson, J.A. Levine, R.T. Whitaker. “Lattice cleaving: a multimaterial tetrahedral meshing algorithm with guarantees,” In IEEE Transactions on Visualization and Computer Graphics (TVCG), pp. 223--237. 2014.
DOI: 10.1109/TVCG.2013.115
PubMed ID: 24356365

ABSTRACT

We introduce a new algorithm for generating tetrahedral meshes that conform to physical boundaries in volumetric domains consisting of multiple materials. The proposed method allows for an arbitrary number of materials, produces high-quality tetrahedral meshes with upper and lower bounds on dihedral angles, and guarantees geometric fidelity. Moreover, the method is combinatoric so its implementation enables rapid mesh construction. These meshes are structured in a way that also allows grading, to reduce element counts in regions of homogeneity. Additionally, we provide proofs showing that both element quality and geometric fidelity are bounded using this approach.



S. Eichelbaum, M. Dannhauer, M. Hlawitschka , D.H. Brooks, T.R. Knosche, G. Scheuermanna. “Visualizing Simulated Electrical Fields from Electroencephalography and Transcranial Electric Brain Stimulation: A Comparative Evaluation,” In Neuroimage, 2014.
DOI: 10.1016/j.neuroimage.2014.04.085

ABSTRACT

Electrical activity of neuronal populations is a crucial aspect of brain activity. This activity is not measured directly but recorded as electrical potential changes using head surface electrodes (electroencephalogram - EEG). Head surface electrodes can also be deployed to inject electrical currents in order to modulate brain activity (transcranial electric stimulation techniques) for therapeutic and neuroscientific purposes. In electroencephalography and noninvasive electric brain stimulation, electrical fields mediate between electrical signal sources and regions of interest (ROI). These fields can be very complicated in structure, and are influenced in a complex way by the conductivity profile of the human head. Visualization techniques play a central role to grasp the nature of those fields because such techniques allow for an effective conveyance of complex data and enable quick qualitative and quantitative assessments. The examination of volume conduction effects of particular head model parameterizations (e.g., skull thickness and layering), of brain anomalies (e.g., holes in the skull, tumors), location and extent of active brain areas (e.g., high concentrations of current densities) and around current injecting electrodes can be investigated using visualization. Here, we evaluate a number of widely used visualization techniques, based on either the potential distribution or on the current-flow. In particular, we focus on the extractability of quantitative and qualitative information from the obtained images, their effective integration of anatomical context information, and their interaction. We present illustrative examples from clinically and neuroscientifically relevant cases and discuss the pros and cons of the various visualization techniques.

Keywords: Visualization, Bioelectric Field, EEG, tDCS, Human Brain



B. Erem P.M. van Dam, D.H. Brooks. “Identifying model inaccuracies and solution uncertainties in noninvasive activation-based imaging of cardiac excitation using convex relaxation,” In IEEE Trans Med Imaging, Vol. 33, No. 4, pp. 902--912. 2014.
DOI: 10.1109/TMI.2014.2297952
PubMed ID: 24710159
PubMed Central ID: PMC3982205

ABSTRACT

Noninvasive imaging of cardiac electrical function has begun to move towards clinical adoption. Here, we consider one common formulation of the problem, in which the goal is to estimate the spatial distribution of electrical activation times during a cardiac cycle. We address the challenge of understanding the robustness and uncertainty of solutions to this formulation. This formulation poses a nonconvex, nonlinear least squares optimization problem. We show that it can be relaxed to be convex, at the cost of some degree of physiological realism of the solution set, and that this relaxation can be used as a framework to study model inaccuracy and solution uncertainty. We present two examples, one using data from a healthy human subject and the other synthesized with the ECGSIM software package. In the first case, we consider uncertainty in the initial guess and regularization parameter. In the second case, we mimic the presence of an ischemic zone in the heart in a way which violates a model assumption. We show that the convex relaxation allows understanding of spatial distribution of parameter sensitivity in the first case, and identification of model violation in the second.



B. Erem, J. Coll-Font, R.M. Orellana, P. Stovicek, D.H. Brooks. “Using transmural regularization and dynamic modeling for noninvasive cardiac potential imaging of endocardial pacing with imprecise thoracic geometry,” In IEEE Trans Med Imaging, Vol. 33, No. 3, pp. 726--738. 2014.
DOI: 10.1109/TMI.2013.2295220
PubMed ID: 24595345
PubMed Central ID: PMC3950945

ABSTRACT

Cardiac electrical imaging from body surface potential measurements is increasingly being seen as a technology with the potential for use in the clinic, for example for pre-procedure planning or during-treatment guidance for ventricular arrhythmia ablation procedures. However several important impediments to widespread adoption of this technology remain to be effectively overcome. Here we address two of these impediments: the difficulty of reconstructing electric potentials on the inner (endocardial) as well as outer (epicardial) surfaces of the ventricles, and the need for full anatomical imaging of the subject's thorax to build an accurate subject-specific geometry. We introduce two new features in our reconstruction algorithm: a nonlinear low-order dynamic parameterization derived from the measured body surface signals, and a technique to jointly regularize both surfaces. With these methodological innovations in combination, it is possible to reconstruct endocardial activation from clinically acquired measurements with an imprecise thorax geometry. In particular we test the method using body surface potentials acquired from three subjects during clinical procedures where the subjects' hearts were paced on their endocardia using a catheter device. Our geometric models were constructed using a set of CT scans limited in axial extent to the immediate region near the heart. The catheter system provides a reference location to which we compare our results. We compare our estimates of pacing site localization, in terms of both accuracy and stability, to those reported in a recent clinical publication , where a full set of CT scans were available and only epicardial potentials were reconstructed.



T. Fogal, F. Proch, A. Schiewe, O. Hasemann, A. Kempf, J. Krüger. “Freeprocessing: Transparent in situ visualization via data interception,” In Proceedings of the 14th Eurographics Conference on Parallel Graphics and Visualization, EGPGV, Eurographics Association, 2014.

ABSTRACT

In situ visualization has become a popular method for avoiding the slowest component of many visualization pipelines: reading data from disk. Most previous in situ work has focused on achieving visualization scalability on par with simulation codes, or on the data movement concerns that become prevalent at extreme scales. In this work, we consider in situ analysis with respect to ease of use and programmability. We describe an abstraction that opens up new applications for in situ visualization, and demonstrate that this abstraction and an expanded set of use cases can be realized without a performance cost.



Y. Gur, C.R. Johnson. “Generalized HARDI Invariants by Method of Tensor Contraction,” In Proceedings of the 2014 IEEE International Symposium on Biomedical Imaging (ISBI), pp. 718--721. April, 2014.

ABSTRACT

We propose a 3D object recognition technique to construct rotation invariant feature vectors for high angular resolution diffusion imaging (HARDI). This method uses the spherical harmonics (SH) expansion and is based on generating rank-1 contravariant tensors using the SH coefficients, and contracting them with covariant tensors to obtain invariants. The proposed technique enables the systematic construction of invariants for SH expansions of any order using simple mathematical operations. In addition, it allows construction of a large set of invariants, even for low order expansions, thus providing rich feature vectors for image analysis tasks such as classification and segmentation. In this paper, we use this technique to construct feature vectors for eighth-order fiber orientation distributions (FODs) reconstructed using constrained spherical deconvolution (CSD). Using simulated and in vivo brain data, we show that these invariants are robust to noise, enable voxel-wise classification, and capture meaningful information on the underlying white matter structure.

Keywords: Diffusion MRI, HARDI, invariants



C.D. Hansen, M. Chen, C.R. Johnson, A.E. Kaufman, H. Hagen (Eds.). “Scientific Visualization: Uncertainty, Multifield, Biomedical, and Scalable Visualization,” Mathematics and Visualization, Springer, 2014.
ISBN: 978-1-4471-6496-8



S. Kurugol, K. Kose, B. Park, J.G. Dy, D.H. Brooks, M. Rajadhyaksha. “Automated Delineation of Dermal-Epidermal Junction In Reflectance Confocal Microscopy Image Stacks Of Human Skin,” In Journal of Investigative Dermatology, September, 2014.
DOI: 10.1038/jid.2014.379
PubMed ID: 25184959

ABSTRACT

Reflectance confocal microscopy (RCM) images skin non-invasively, with optical sectioning and nuclear-level resolution comparable to that of pathology. Based on assessment of the dermal-epidermal junction (DEJ) and morphologic features in its vicinity, skin cancer can be diagnosed in vivo with high sensitivity and specificity. However, the current visual, qualitative approach for reading images leads to subjective variability in diagnosis. We hypothesize that machine learning-based algorithms may enable a more quantitative, objective approach. Testing and validation was performed with two algorithms that can automatically delineate the DEJ in RCM stacks of normal human skin. The test set was composed of 15 fair and 15 dark skin stacks (30 subjects) with expert labellings. In dark skin, in which the contrast is high due to melanin, the algorithm produced an average error of 7.9±6.4 μm. In fair skin, the algorithm delineated the DEJ as a transition zone, with average error of 8.3±5.8 μm for the epidermis-to-transition zone boundary and 7.6±5.6 μm for the transition zone-to-dermis. Our results suggest that automated algorithms may quantitatively guide the delineation of the DEJ, to assist in objective reading of RCM images. Further development of such algorithms may guide assessment of abnormal morphological features at the DEJ.



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. Dibella, D. Parker, R.S. MacLeod, N.F. Marrouche. “Atrial fibrillation ablation outcome is predicted by left atrial remodeling on MRI,” In Circ Arrhythm Electrophysiol, Vol. 7, No. 1, pp. 23--30. 2014.
DOI: 10.1161/CIRCEP.113.000689
PubMed ID: 24363354

ABSTRACT

BACKGROUND:
Although 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 MRI (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 patients with AF without contraindications to MRI before undergoing their first ablation procedure and on 21 non-AF control subjects. Patients were categorized by SRM stage (I-IV) based on the percentage of LA wall enhancement for correlation with procedure outcomes. Histological validation of SRM was performed comparing LGE-MRI with surgical biopsy. A total of 386 patients (91%) with adequate LGE-MRI scans were included in the study. After ablation, 123 patients (31.9%) experienced recurrent atrial arrhythmias during the 1-year follow-up. Recurrent arrhythmias (failed ablations) occurred at higher SRM stages with 28 of 133 (21.0%) in stage I, 40 of 140 (29.3%) in stage II, 24 of 71 (33.8%) in stage III, and 30 of 42 (71.4%) in stage IV. In multivariate analysis, ablation outcome was best predicted by advanced SRM stage (hazard ratio, 4.89; P