The NIH/NIGMS
Center for Integrative Biomedical Computing

SCI Publications

2021


P. Agrawal, R. T. Whitaker, S. Y. Elhabian. “Learning Deep Features for Shape Correspondence with Domain Invariance,” Subtitled “arXiv preprint arXiv:2102.10493,” 2021.

ABSTRACT

Correspondence-based shape models are key to various medical imaging applications that rely on a statistical analysis of anatomies. Such shape models are expected to represent consistent anatomical features across the population for population-specific shape statistics. Early approaches for correspondence placement rely on nearest neighbor search for simpler anatomies. Coordinate transformations for shape correspondence hold promise to address the increasing anatomical complexities. Nonetheless, due to the inherent shape-level geometric complexity and population-level shape variation, the coordinate-wise correspondence often does not translate to the anatomical correspondence. An alternative, group-wise approach for correspondence placement explicitly models the trade-off between geometric description and the population's statistical compactness. However, these models achieve limited success in resolving nonlinear shape correspondence. Recent works have addressed this limitation by adopting an application-specific notion of correspondence through lifting positional data to a higher dimensional feature space. However, they heavily rely on manual expertise to create domain-specific features and consistent landmarks. This paper proposes an automated feature learning approach, using deep convolutional neural networks to extract correspondence-friendly features from shape ensembles. Further, an unsupervised domain adaptation scheme is introduced to augment the pretrained geometric features with new anatomies. Results on anatomical datasets of human scapula, femur, and pelvis bones demonstrate that …



J. A. Bergquist, W. W. Good, B. Zenger, J. D. Tate, L. C. Rupp, R. S. MacLeod. “The Electrocardiographic Forward Problem: A Benchmark Study,” In Computers in Biology and Medicine, Vol. 134, Pergamon, pp. 104476. 2021.
DOI: https://doi.org/10.1016/j.compbiomed.2021.104476

ABSTRACT

Background
Electrocardiographic forward problems are crucial components for noninvasive electrocardiographic imaging (ECGI) that compute torso potentials from cardiac source measurements. Forward problems have few sources of error as they are physically well posed and supported by mature numerical and computational techniques. However, the residual errors reported from experimental validation studies between forward computed and measured torso signals remain surprisingly high.

Objective
To test the hypothesis that incomplete cardiac source sampling, especially above the atrioventricular (AV) plane is a major contributor to forward solution errors.

Methods
We used a modified Langendorff preparation suspended in a human-shaped electrolytic torso-tank and a novel pericardiac-cage recording array to thoroughly sample the cardiac potentials. With this carefully controlled experimental preparation, we minimized possible sources of error, including geometric error and torso inhomogeneities. We progressively removed recorded signals from above the atrioventricular plane to determine how the forward-computed torso-tank potentials were affected by incomplete source sampling.

Results
We studied 240 beats total recorded from three different activation sequence types (sinus, and posterior and anterior left-ventricular free-wall pacing) in each of two experiments. With complete sampling by the cage electrodes, all correlation metrics between computed and measured torso-tank potentials were above 0.93 (maximum 0.99). The mean root-mean-squared error across all beat types was also low, less than or equal to 0.10 mV. A precipitous drop in forward solution accuracy was observed when we included only cage measurements below the AV plane.

Conclusion
First, our forward computed potentials using complete cardiac source measurements set a benchmark for similar studies. Second, this study validates the importance of complete cardiac source sampling above the AV plane to produce accurate forward computed torso potentials. Testing ECGI systems and techniques with these more complete and highly accurate datasets will improve inverse techniques and noninvasive detection of cardiac electrical abnormalities.



R. Bhalodia, S. Elhabian, L. Kavan, R. Whitaker. “Leveraging Unsupervised Image Registration for Discovery of Landmark Shape Descriptor,” In Medical Image Analysis, Elsevier, pp. 102157. 2021.

ABSTRACT

In current biological and medical research, statistical shape modeling (SSM) provides an essential framework for the characterization of anatomy/morphology. Such analysis is often driven by the identification of a relatively small number of geometrically consistent features found across the samples of a population. These features can subsequently provide information about the population shape variation. Dense correspondence models can provide ease of computation and yield an interpretable low-dimensional shape descriptor when followed by dimensionality reduction. However, automatic methods for obtaining such correspondences usually require image segmentation followed by significant preprocessing, which is taxing in terms of both computation as well as human resources. In many cases, the segmentation and subsequent processing require manual guidance and anatomy specific domain expertise. This paper proposes a self-supervised deep learning approach for discovering landmarks from images that can directly be used as a shape descriptor for subsequent analysis. We use landmark-driven image registration as the primary task to force the neural network to discover landmarks that register the images well. We also propose a regularization term that allows for robust optimization of the neural network and ensures that the landmarks uniformly span the image domain. The proposed method circumvents segmentation and preprocessing and directly produces a usable shape descriptor using just 2D or 3D images. In addition, we also propose two variants on the training loss function that allows for prior shape information to be integrated into the model. We apply this framework on several 2D and 3D datasets to obtain their shape descriptors. We analyze these shape descriptors in their efficacy of capturing shape information by performing different shape-driven applications depending on the data ranging from shape clustering to severity prediction to outcome diagnosis.



R. Bhalodia, S. Elhabian, J. Adams, W. Tao, L. Kavan, R. Whitaker. “DeepSSM: A Blueprint for Image-to-Shape Deep Learning Models,” Subtitled “arXiv preprint arXiv:2110.07152,” 2021.

ABSTRACT

Statistical shape modeling (SSM) characterizes anatomical variations in a population of shapes generated from medical images. SSM requires consistent shape representation across samples in shape cohort. Establishing this representation entails a processing pipeline that includes anatomy segmentation, re-sampling, registration, and non-linear optimization. These shape representations are then used to extract low-dimensional shape descriptors that facilitate subsequent analyses in different applications. However, the current process of obtaining these shape descriptors from imaging data relies on human and computational resources, requiring domain expertise for segmenting anatomies of interest. Moreover, this same taxing pipeline needs to be repeated to infer shape descriptors for new image data using a pre-trained/existing shape model. Here, we propose DeepSSM, a deep learning-based framework for learning the functional mapping from images to low-dimensional shape descriptors and their associated shape representations, thereby inferring statistical representation of anatomy directly from 3D images. Once trained using an existing shape model, DeepSSM circumvents the heavy and manual pre-processing and segmentation and significantly improves the computational time, making it a viable solution for fully end-to-end SSM applications. In addition, we introduce a model-based data-augmentation strategy to address data scarcity. Finally, this paper presents and analyzes two different architectural variants of DeepSSM with different loss functions using three medical datasets and their downstream clinical application. Experiments showcase that DeepSSM performs comparably or better to the state-of-the-art SSM both quantitatively and on application-driven downstream tasks. Therefore, DeepSSM aims to provide a comprehensive blueprint for deep learning-based image-to-shape models.



S. R. Black, A. Janson, M. Mahan, J. Anderson, C. R. Butson. “Identification of Deep Brain Stimulation Targets for Neuropathic Pain After Spinal Cord Injury Using Localized Increases in White Matter Fiber Cross‐Section,” In Neuromodulation: Technology at the Neural Interface, John Wiley & Sons, Inc., 2021.

ABSTRACT

Objectives
The spinal cord injury (SCI) patient population is overwhelmingly affected by neuropathic pain (NP), a secondary condition for which therapeutic options are limited and have a low degree of efficacy. The objective of this study was to identify novel deep brain stimulation (DBS) targets that may theoretically benefit those with NP in the SCI patient population. We hypothesize that localized changes in white matter identified in SCI subjects with NP compared to those without NP could be used to develop an evidence‐based approach to DBS target identification.

Materials and Methods
To classify localized neurostructural changes associated with NP in the SCI population, we compared white matter fiber density (FD) and cross‐section (FC) between SCI subjects with NP (N = 17) and SCI subjects without NP (N = 15) using diffusion‐weighted magnetic resonance imaging (MRI). We then identified theoretical target locations for DBS using fiber bundles connected to significantly altered regions of white matter. Finally, we used computational models of DBS to determine if our theoretical target locations could be used to feasibly activate our fiber bundles of interest.
Results
We identified significant increases in FC in the splenium of the corpus callosum in pain subjects when compared to controls. We then isolated five fiber bundles that were directly connected to the affected region of white matter. Our models were able to predict that our fiber bundles of interest can be feasibly activated with DBS at reasonable stimulation amplitudes and with clinically relevant implantation approaches.
Conclusions
Altogether, we identified neuroarchitectural changes associated with NP in the SCI cohort and implemented a novel, evidence‐driven target selection approach for DBS to guide future research in neuromodulation treatment of NP after SCI.



W. W. Good, B. Zenger, J. A. Bergquist, L. C. Rupp, K. K. Gillette, M. A.F. Gsell, G. Plank, R. S. MacLeod. “Quantifying the spatiotemporal influence of acute myocardial ischemia on volumetric conduction velocity,” In Journal of Electrocardiology, Vol. 66, Churchill Livingstone, pp. 86-94. 2021.

ABSTRACT

Introduction
Acute myocardial ischemia occurs when coronary perfusion to the heart is inadequate, which can perturb the highly organized electrical activation of the heart and can result in adverse cardiac events including sudden cardiac death. Ischemia is known to influence the ST and repolarization phases of the ECG, but it also has a marked effect on propagation (QRS); however, studies investigating propagation during ischemia have been limited.

Methods
We estimated conduction velocity (CV) and ischemic stress prior to and throughout 20 episodes of experimentally induced ischemia in order to quantify the progression and correlation of volumetric conduction changes during ischemia. To estimate volumetric CV, we 1) reconstructed the activation wavefront; 2) calculated the elementwise gradient to approximate propagation direction; and 3) estimated conduction speed (CS) with an inverse-gradient technique.
Results
We found that acute ischemia induces significant conduction slowing, reducing the global median speed by 20 cm/s. We observed a biphasic response in CS (acceleration then deceleration) early in some ischemic episodes. Furthermore, we noted a high temporal correlation between ST-segment changes and CS slowing; however, when comparing these changes over space, we found only moderate correlation (corr. = 0.60).
Discussion
This study is the first to report volumetric CS changes (acceleration and slowing) during episodes of acute ischemia in the whole heart. We showed that while CS changes progress in a similar time course to ischemic stress (measured by ST-segment shifts), the spatial overlap is complex and variable, showing extreme conduction slowing both in and around regions experiencing severe ischemia.



W. W. Good, K. Gillette, B. Zenger, J. Bergquist, L. C. Rupp, J. D. Tate, D. Anderson, M. Gsell, G. Plank, R. S. Macleod. “Estimation and validation of cardiac conduction velocity and wavefront reconstruction using epicardial and volumetric data,” In IEEE Transactions on Biomedical Engineering, IEEE, 2021.
DOI: 10.1109/TBME.2021.3069792

ABSTRACT

Objective: In this study, we have used whole heart simulations parameterized with large animal experiments to validate three techniques (two from the literature and one novel) for estimating epicardial and volumetric conduction velocity (CV). Methods: We used an eikonal-based simulation model to generate ground truth activation sequences with prescribed CVs. Using the sampling density achieved experimentally we examined the accuracy with which we could reconstruct the wavefront, and then examined the robustness of three CV estimation techniques to reconstruction related error. We examined a triangulation-based, inverse-gradient-based, and streamline-based techniques for estimating CV cross the surface and within the volume of the heart. Results: The reconstructed activation times agreed closely with simulated values, with 50-70% of the volumetric nodes and 97-99% of the epicardial nodes were within 1 ms of the ground truth. We found close agreement between the CVs calculated using reconstructed versus ground truth activation times, with differences in the median estimated CV on the order of 3-5% volumetrically and 1-2% superficially, regardless of what technique was used. Conclusion: Our results indicate that the wavefront reconstruction and CV estimation techniques are accurate, allowing us to examine changes in propagation induced by experimental interventions such as acute ischemia, ectopic pacing, or drugs. Significance: We implemented, validated, and compared the performance of a number of CV estimation techniques. The CV estimation techniques implemented in this study produce accurate, high-resolution CV fields that can be used to study propagation in the heart experimentally and clinically.



W. W. Good, B. Zenger, J. A. Bergquist, L. C. Rupp, K. Gillett, N. Angel, D. Chou, G. Plank, R. S. MacLeod. “Combining endocardial mapping and electrocardiographic imaging (ECGI) for improving PVC localization: A feasibility study,” In Journal of Electrocardiology, 2021.
ISSN: 0022-0736
DOI: https://doi.org/10.1016/j.jelectrocard.2021.08.013

ABSTRACT

Introduction

Accurate reconstruction of cardiac activation wavefronts is crucial for clinical diagnosis, management, and treatment of cardiac arrhythmias. Furthermore, reconstruction of activation profiles within the intramural myocardium has long been impossible because electrical mapping was only performed on the endocardial surface. Recent advancements in electrocardiographic imaging (ECGI) have made endocardial and epicardial activation mapping possible. We propose a novel approach to use both endocardial and epicardial mapping in a combined approach to reconstruct intramural activation times.

Objective

To implement and validate a combined epicardial/endocardial intramural activation time reconstruction technique.
Methods

We used 11 simulations of ventricular activation paced from sites throughout myocardial wall and extracted endocardial and epicardial activation maps at approximate clinical resolution. From these maps, we interpolated the activation times through the myocardium using thin-plate-spline radial basis functions. We evaluated activation time reconstruction accuracy using root-mean-squared error (RMSE) of activation times and the percent of nodes within 1 ms of the ground truth.
Results

Reconstructed intramural activation times showed an RMSE and percentage of nodes within 1 ms of the ground truth simulations of 3 ms and 70%, respectively. In the worst case, the RMSE and percentage of nodes were 4 ms and 60%, respectively.
Conclusion

We showed that a simple, yet effective combination of clinical endocardial and epicardial activation maps can accurately reconstruct intramural wavefronts. Furthermore, we showed that this approach provided robust reconstructions across multiple intramural stimulation sites.



X. Jiang, J. C. Font, J. A. Bergquist, B. Zenger, W. W. Good, D. H. Brooks, R. S. MacLeod, L. Wang. “Deep Adaptive Electrocardiographic Imaging with Generative Forward Model for Error Reduction,” In Functional Imaging and Modeling of the Heart: 11th International Conference, In Functional Imaging and Modeling of the Heart: 11th International Conference, Vol. 12738, Springer Nature, pp. 471. 2021.

ABSTRACT

Accuracy of estimating the heart’s electrical activity with Electrocardiographic Imaging (ECGI) is challenging due to using an error-prone physics-based model (forward model). While getting better results than the traditional numerical methods following the underlying physics, modern deep learning approaches ignore the physics behind the electrical propagation in the body and do not allow the use of patientspecific geometry. We introduce a deep-learning-based ECGI framework capable of understanding the underlying physics, aware of geometry, and adjustable to patient-specific data. Using a variational autoencoder (VAE), we uncover the forward model’s parameter space, and when solving the inverse problem, these parameters will be optimized to reduce the errors in the forward model. In both simulation and real data experiments, we demonstrated the ability of the presented framework to provide accurate reconstruction of the heart’s electrical potentials and localization of the earliest activation sites.



R. Kamali, J. Kump, E. Ghafoori, M. Lange, N. Hu, T. J. Bunch, D. J. Dosdall, R. S. Macleod, R. Ranjan. “Area Available for Atrial Fibrillation to Propagate Is an Important Determinant of Recurrence After Ablation,” In JACC: Clinical Electrophysiology, Elsevier, 2021.

ABSTRACT

This study sought to evaluate atrial fibrillation (AF) ablation outcomes based on scar patterns and contiguous area available for AF wavefronts to propagate.



A.S. Rababah, L.R. Bear, Y.S. Dogrusoz, W. Good, J. Bergquist, J. Stoks, R. MacLeod, K. Rjoob, M. Jennings, J. Mclaughlin, D. D. Finlay. “Reducing Line-of-block Artifacts in Cardiac Activation Maps Estimated Using ECG Imaging: A Comparison of Source Models and Estimation Methods,” In Computers in Biology and Medicine, Vol. 136, pp. 104666. 2021.

ABSTRACT

Electrocardiographic imaging is an imaging modality that has been introduced recently to help in visualizing the electrical activity of the heart and consequently guide the ablation therapy for ventricular arrhythmias. One of the main challenges of this modality is that the electrocardiographic signals recorded at the torso surface are contaminated with noise from different sources. Low amplitude leads are more affected by noise due to their low peak-to-peak amplitude. In this paper, we have studied 6 datasets from two torso tank experiments (Bordeaux and Utah experiments) to investigate the impact of removing or interpolating these low amplitude leads on the inverse reconstruction of cardiac electrical activity. Body surface potential maps used were calculated by using the full set of recorded leads, removing 1, 6, 11, 16, or 21 low amplitude leads, or interpolating 1, 6, 11, 16, or 21 low amplitude leads using one of the three interpolation methods – Laplacian interpolation, hybrid interpolation, or the inverse-forward interpolation. The epicardial potential maps and activation time maps were computed from these body surface potential maps and compared with those recorded directly from the heart surface in the torso tank experiments. There was no significant change in the potential maps and activation time maps after the removal of up to 11 low amplitude leads. Laplacian interpolation and hybrid interpolation improved the inverse reconstruction in some datasets and worsened it in the rest. The inverse forward interpolation of low amplitude leads improved it in two out of 6 datasets and at least remained the same in the other datasets. It was noticed that after doing the inverse-forward interpolation, the selected lambda value was closer to the optimum lambda value that gives the inverse solution best correlated with the recorded one.



J. Salinet, R. Molero, F. S. Schlindwein, J. Karel, M. Rodrigo, J. L. Rojo-Álvarez, O. Berenfeld, A. M. Climent, B. Zenger, F. Vanheusden, J. G. S. Paredes, R. MacLeod, F. Atienza, M. S. Guillem, M. Cluitmans, P. Bonizzi. “Electrocardiographic imaging for atrial fibrillation: a perspective from computer models and animal experiments to clinical value,” In Frontiers in Physiology, Vol. 12, Frontiers Media, April, 2021.
DOI: 10.3389/fphys.2021.653013

ABSTRACT

Salinet et al. Electrocardiographic Imaging for Atrial Fibrillation treatment guidance (for example, localization of AF triggers and sustaining mechanisms), and we discuss the technological requirements and validation. We address experimental and clinical results, limitations, and future challenges for fruitful application of ECGI for AF understanding and management. We pay attention to existing techniques and clinical application, to computer models and (animal or human) experiments, to challenges of methodological and clinical validation. The overall objective of the study is to provide a consensus on valuable directions that ECGI research may take to provide future improvements in AF characterization and treatment guidance.



S. Sane, A. Yenpure, R. Bujack, M. Larsen, K. Moreland, C. Garth, C. R. Johnson,, H. Childs. “Scalable In Situ Computation of Lagrangian Representations via Local Flow Maps,” In Eurographics Symposium on Parallel Graphics and Visualization, The Eurographics Association, 2021.
DOI: 10.2312/pgv.20211040

ABSTRACT

In situ computation of Lagrangian flow maps to enable post hoc time-varying vector field analysis has recently become an active area of research. However, the current literature is largely limited to theoretical settings and lacks a solution to address scalability of the technique in distributed memory. To improve scalability, we propose and evaluate the benefits and limitations of a simple, yet novel, performance optimization. Our proposed optimization is a communication-free model resulting in local Lagrangian flow maps, requiring no message passing or synchronization between processes, intrinsically improving scalability, and thereby reducing overall execution time and alleviating the encumbrance placed on simulation codes from communication overheads. To evaluate our approach, we computed Lagrangian flow maps for four time-varying simulation vector fields and investigated how execution time and reconstruction accuracy are impacted by the number of GPUs per compute node, the total number of compute nodes, particles per rank, and storage intervals. Our study consisted of experiments computing Lagrangian flow maps with up to 67M particle trajectories over 500 cycles and used as many as 2048 GPUs across 512 compute nodes. In all, our study contributes an evaluation of a communication-free model as well as a scalability study of computing distributed Lagrangian flow maps at scale using in situ infrastructure on a modern supercomputer.



J. D. Tate, W. W. Good, N. Zemzemi, M. Boonstra, P. van Dam, D. H. Brooks, A. Narayan, R. S. MacLeod. “Uncertainty Quantification of the Effects of Segmentation Variability in ECGI,” In Functional Imaging and Modeling of the Heart, Springer International Publishing, pp. 515--522. 2021.
DOI: 10.1007/978-3-030-78710-3_49

ABSTRACT

Despite advances in many of the techniques used in Electrocardiographic Imaging (ECGI), uncertainty remains insufficiently quantified for many aspects of the pipeline. The effect of geometric uncertainty, particularly due to segmentation variability, may be the least explored to date. We use statistical shape modeling and uncertainty quantification (UQ) to compute the effect of segmentation variability on ECGI solutions. The shape model was made with Shapeworks from nine segmentations of the same patient and incorporated into an ECGI pipeline. We computed uncertainty of the pericardial potentials and local activation times (LATs) using polynomial chaos expansion (PCE) implemented in UncertainSCI. Uncertainty in pericardial potentials from segmentation variation mirrored areas of high variability in the shape model, near the base of the heart and the right ventricular outflow tract, and that ECGI was less sensitive to uncertainty in the posterior region of the heart. Subsequently LAT calculations could vary dramatically due to segmentation variability, with a standard deviation as high as 126ms, yet mainly in regions with low conduction velocity. Our shape modeling and UQ pipeline presented possible uncertainty in ECGI due to segmentation variability and can be used by researchers to reduce said uncertainty or mitigate its effects. The demonstrated use of statistical shape modeling and UQ can also be extended to other types of modeling pipelines.



V. Vedam-Mai, K. Deisseroth, J. Giordano, G. Lazaro-Munoz, W. Chiong, N. Suthana, J. Langevin, J. Gill, W. Goodman, N. R. Provenza, C. H. Halpern, R. S. Shivacharan, T. N. Cunningham, S. A. Sheth, N. Pouratian, K. W. Scangos, H. S. Mayberg, A. Horn, K. A. Johnson, C. R. Butson, R. Gilron, C. de Hemptinne, R. Wilt, M. Yaroshinsky, S. Little, P. Starr, G. Worrell, P. Shirvalkar, E. Chang, J. Volkmann, M. Muthuraman, S. Groppa, A. A. Kühn, L. Li, M. Johnson, K. J. Otto, R. Raike, S. Goetz, C. Wu, P. Silburn, B. Cheeran, Y. J. Pathak, M. Malekmohammadi, A. Gunduz, J. K. Wong, S. Cernera, A. W. Shukla, A. Ramirez-Zamora, W. Deeb, A. Patterson, K. D. Foote, M. S. Okun. “Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies,” In Frontiers in Human Neuroscience, Vol. 15, pp. 169. 2021.
ISSN: 1662-5161
DOI: 10.3389/fnhum.2021.644593

ABSTRACT

We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer’s disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank.



Y. Wan, H.A. Holman, C. Hansen. “Interactive Analysis for Large Volume Data from Fluorescence Microscopy at Cellular Precision,” In Computers & Graphics, Vol. 98, Pergamon, pp. 138-149. 2021.
DOI: https://doi.org/10.1016/j.cag.2021.05.006

ABSTRACT

The main objective for understanding fluorescence microscopy data is to investigate and evaluate the fluorescent signal intensity distributions as well as their spatial relationships across multiple channels. The quantitative analysis of 3D fluorescence microscopy data needs interactive tools for researchers to select and focus on relevant biological structures. We developed an interactive tool based on volume visualization techniques and GPU computing for streamlining rapid data analysis. Our main contribution is the implementation of common data quantification functions on streamed volumes, providing interactive analyses on large data without lengthy preprocessing. Data segmentation and quantification are coupled with brushing and executed at an interactive speed. A large volume is partitioned into data bricks, and only user-selected structures are analyzed to constrain the computational load. We designed a framework to assemble a sequence of GPU programs to handle brick borders and stitch analysis results. Our tool was developed in collaboration with domain experts and has been used to identify cell types. We demonstrate a workflow to analyze cells in vestibular epithelia of transgenic mice.



B. Zenger, W. W. Good, J. A. Bergquist, L. C. Rupp, M. Perez, G. J. Stoddard, V. Sharma, R. S. MacLeod. “Transient recovery of epicardial and torso ST-segment ischemic signals during cardiac stress tests: A possible physiological mechanism,” In Journal of Electrocardiology, Churchill Livingstone, 2021.

ABSTRACT

Background

Acute myocardial ischemia has several characteristic ECG findings, including clinically detectable ST-segment deviations. However, the sensitivity and specificity of diagnosis based on ST-segment changes are low. Furthermore, ST-segment deviations have been shown to be transient and spontaneously recover without any indication the ischemic event has subsided.

Objective

Assess the transient recovery of ST-segment deviations on remote recording electrodes during a partial occlusion cardiac stress test and compare them to intramyocardial ST-segment deviations.

Methods

We used a previously validated porcineBZ experimental model of acute myocardial ischemia with controllable ischemic load and simultaneous electrical measurements within the heart wall, on the epicardial surface, and on the torso surface. Simulated cardiac stress tests were induced by occluding a coronary artery while simultaneously pacing rapidly or infusing dobutamine to stimulate cardiac function. Postexperimental imaging created anatomical models for data visualization and quantification. Markers of ischemia were identified as deviations in the potentials measured at 40% of the ST-segment. Intramural cardiac conduction speed was also determined using the inverse gradient method. We assessed changes in intramyocardial ischemic volume proportion, conduction speed, clinical presence of ischemia on remote recording arrays, and regional changes to intramyocardial ischemia. We defined the peak deviation response time as the time interval after onset of ischemia at which maximum ST-segment deviation was achieved, and ST-recovery time was the interval when ST deviation returned to below thresholded of ST elevation.

Results

In both epicardial and torso recordings, the peak ST-segment deviation response time was 4.9±1.1 min and the ST-recovery time was approximately 7.9±2.5 min, both well before the termination of the ischemic stress. At peak response time, conduction speed was reduced by 50% and returned to near baseline at ST-recovery. The overall ischemic volume proportion initially increased, on average, to 37% at peak response time; however, it recovered only to 30% at the ST-recovery time. By contrast, the subepicardial region of the myocardial wall showed 40% ischemic volume at peak response time and recovered much more strongly to 25% as epicardial ST-segment deviations returned to baseline.

Conclusion

Our data show that remote ischemic signal recovery correlates with a recovery of the subepicardial myocardium, while subendocardial ischemic development persists.



L. Zhou, C. R. Johnson, D. Weiskopf. “Data-Driven Space-Filling Curves,” In IEEE Transactions on Visualization and Computer Graphics, Vol. 27, No. 2, IEEE, pp. 1591-1600. 2021.
DOI: 10.1109/TVCG.2020.3030473

ABSTRACT

We propose a data-driven space-filling curve method for 2D and 3D visualization. Our flexible curve traverses the data elements in the spatial domain in a way that the resulting linearization better preserves features in space compared to existing methods. We achieve such data coherency by calculating a Hamiltonian path that approximately minimizes an objective function that describes the similarity of data values and location coherency in a neighborhood. Our extended variant even supports multiscale data via quadtrees and octrees. Our method is useful in many areas of visualization, including multivariate or comparative visualization,ensemble visualization of 2D and 3D data on regular grids, or multiscale visual analysis of particle simulations. The effectiveness of our method is evaluated with numerical comparisons to existing techniques and through examples of ensemble and multivariate datasets.


2020


A. P. Janson, D. N. Anderson, C. R. Butson. “Activation robustness with directional leads and multi-lead configurations in deep brain stimulation,” In Journal of Neural Engineering, Vol. 17, No. 2, IOP Publishing, pp. 026012. March, 2020.
DOI: 10.1088/1741-2552/ab7b1d

ABSTRACT

Objective: Clinical outcomes from deep brain stimulation (DBS) can be highly variable, and two critical factors underlying this variability are the location and type of stimulation. In this study we quantified how robustly DBS activates a target region when taking into account a range of different lead designs and realistic variations in placement. The objective of the study is to assess the likelihood of achieving target activation.

Approach: We performed finite element computational modeling and established a metric of performance robustness to evaluate the ability of directional and multi-lead configurations to activate target fiber pathways while taking into account location variability. A more robust lead configuration produces less variability in activation across all stimulation locations around the target.

Main results: Directional leads demonstrated higher overall performance robustness compared to axisymmetric leads, primarily 1-2 mm outside of the target. Multi-lead configurations demonstrated higher levels of robustness compared to any single lead due to distribution of electrodes in a broader region around the target.

Significance: Robustness measures can be used to evaluate the performance of existing DBS lead designs and aid in the development of novel lead designs to better accommodate known variability in lead location and orientation. This type of analysis may also be useful to understand how DBS clinical outcome variability is influenced by lead location among groups of patients.



K. A. Johnson, G. Duffley, D. Nesterovich Anderson, J. L. Ostrem, M. Welter, J. C. Baldermann, J. Kuhn, D. Huys, V. Visser-Vandewalle, T. Foltynie, L. Zrinzo, M. Hariz, A. F. G. Leentjens, A. Y. Mogilner, M. H. Pourfar, L. Almeida, A. Gunduz, K. D. Foote, M. S. Okun, C. R. Butson. “Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome,” In Brain, July, 2020.
ISSN: 0006-8950
DOI: 10.1093/brain/awaa188

ABSTRACT

Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate ‘reverse’ tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P < 0.017). For centromedial thalamus, connectivity to sensorimotor networks, parietal-temporal-occipital networks, putamen, and cerebellum was positively correlated with tic improvement; the model predicted clinical improvement scores (P = 0.012) and was robust to cross-validation. Regions in the anterior/lateral centromedial thalamus exhibited higher connectivity to the positively correlated networks, but volume of tissue activated overlap with this map did not predict improvement (P > 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.