Designed especially for neurobiologists, FluoRender is an interactive tool for multi-channel fluorescence microscopy data visualization and analysis.
Deep brain stimulation
BrainStimulator is a set of networks that are used in SCIRun to perform simulations of brain stimulation such as transcranial direct current stimulation (tDCS) and magnetic transcranial stimulation (TMS).
Developing software tools for science has always been a central vision of the SCI Institute.

SCI Publications

2012


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.
DOI: 10.1161/CIRCEP.112.973164
PubMed ID: 23071143
PubMed Central ID: PMC3691079

ABSTRACT

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.



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.
DOI: 10.1109/EMBC.2012.6346648
PubMed ID: 23366609
PubMed Central ID: PMC3652873

ABSTRACT

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.


2011


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.
DOI: 10.1111/j.1540-8167.2010.01876.x
PubMed ID: 20807271

ABSTRACT

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.



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.
DOI: 10.1109/IEMBS.2011.6090052
PubMed ID: 22254301
PubMed Central ID: PMC3337752

ABSTRACT

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.



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



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.
DOI: 10.1109/IEMBS.2011.6091455
PubMed ID: 22255678
PubMed Central ID: PMC3345888

ABSTRACT

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.M. Isaacson, J.G. Stinstra, R.D. Bloebaum, COL P.F. Pasquina, R.S. MacLeod. “Establishing Multiscale Models for Simulating Whole Limb Estimates of Electric Fields for Osseointegrated Implants,” In IEEE Transactions on Biomedical Engineering, Vol. 58, No. 10, pp. 2991--2994. 2011.
DOI: 10.1109/TBME.2011.2160722
PubMed ID: 21712151
PubMed Central ID: PMC3179554

ABSTRACT

Although the survival rates of warfighters in recent conflicts are among the highest in military history, those who have sustained proximal limb amputations may present additional rehabilitation challenges. In some of these cases, traditional prosthetic limbs may not provide adequate function for service members returning to an active lifestyle. Osseointegration has emerged as an acknowledged treatment for those with limited residual limb length and those with skin issues associated with a socket together. Using this technology, direct skeletal attachment occurs between a transcutaneous osseointegrated implant (TOI) and the host bone, thereby eliminating the need for a socket. While reports from the first 100 patients with a TOI have been promising, some rehabilitation regimens require 12-18 months of restricted weight bearing to prevent overloading at the bone-implant interface. Electrically induced osseointegration has been proposed as an option for expediting periprosthetic fixation and preliminary studies have demonstrated the feasibility of adapting the TOI into a functional cathode. To assure safe and effective electric fields that are conducive for osseoinduction and osseointegration, we have developed multiscale modeling approaches to simulate the expected electric metrics at the bone--implant interface. We have used computed tomography scans and volume segmentation tools to create anatomically accurate models that clearly distinguish tissue parameters and serve as the basis for finite element analysis. This translational computational biological process has supported biomedical electrode design, implant placement, and experiments to date have demonstrated the clinical feasibility of electrically induced osseointegration.



R.S. MacLeod, J.J.E. Blauer. “Atrial Fibrillation,” In Multimodal Cardiovascular Imaging: Principles and Clinical Applications, Ch. 25, Edited by O. Pahlm and G. Wagner, McGraw Hill, 2011.
ISBN: 0071613463

ABSTRACT

Atrial fibrillation (AF) is the most common form of cardiac arrhythmia so that a review of the role imaging in AF is a natural topic to include in this book. Further motivation comes from the fact that the treatment of AF probably includes more different forms of imaging, often merged or combined in a variety of ways, than perhaps any other clinical intervention. A typical clinical electrophysiology lab for the treatment of AF usually contains no less than 6 and often more than 8 individual monitors, each rendering some form of image based information about the patient undergoing therapy. There is naturally great motivation to merge different images and different imaging modalities in the setting of AF but also very challenging because of a host of factors related to the small size, extremely thin walls, the large natural variation in atrial shape, and the fact that fibrillation is occurring so that atrial shape is changing rapidly and irregularly. Thus, the use of multimodal imaging has recently become a very active and challenging area of image processing and analysis research and development, driven by an enormous clinical need to understand and treat a disease that affects some 5 million Americans alone, a number that is predicted to increase to almost 16 million by 2050.

In this chapter we attempt to provide an overview of the large variety of imaging modalities and uses in the management and understanding of atrial fibrillation, with special emphasis on the most novel applications of magnetic resonance imaging (MRI) technology. To provide clinical and biomedical motivation, we outline the basics of the disease together with some contemporary hypotheses about its etiology and management. We then describe briefly the imaging modalities in common use in the management and research of AF, then focus on the use or MRI for all phases of the management of patients with AF and indicate some of the major engineering challenges that can motivate further progress.

Keywords: ablation, carma, cvrti, 5P41-RR012553-10



C.J. McGann, E.G. Kholmovski, J.J. Blauer, S. Vijayakumar, T.S. Haslam, J.E. Cates, E.V. DiBella, N.S. Burgon, B. Wilson, A.J. Alexander, M.W. Prastawa, M. Daccarett, G. Vergara, N.W. Akoum, D.L. Parker, R.S. MacLeod, N.F. Marrouche. “Dark Regions of No-Reflow on Late Gadolinium Enhancement Magnetic Resonance Imaging Result in Scar Formation After Atrial Fibrillation Ablation,” In Journal of the American College of Cardiology, Vol. 58, No. 2, pp. 177--185. 2011.
DOI: 10.1016/j.jacc.2011.04.008
PubMed ID: 21718914

ABSTRACT

Objectives: The aim of this study was to assess acute ablation injuries seen on late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) immediately post-ablation (IPA) and the association with permanent scar 3 months post-ablation (3moPA).

Background: Success rates for atrial fibrillation catheter ablation vary significantly, in part because of limited information about the location, extent, and permanence of ablation injury at the time of procedure. Although the amount of scar on LGE MRI months after ablation correlates with procedure outcomes, early imaging predictors of scar remain elusive.

Methods: Thirty-seven patients presenting for atrial fibrillation ablation underwent high-resolution MRI with a 3-dimensional LGE sequence before ablation, IPA, and 3moPA using a 3-T scanner. The acute left atrial wall injuries on IPA scans were categorized as hyperenhancing (HE) or nonenhancing (NE) and compared with scar 3moPA.

Results: Heterogeneous injuries with HE and NE regions were identified in all patients. Dark NE regions in the left atrial wall on LGE MRI demonstrate findings similar to the \"no-reflow\" phenomenon. Although the left atrial wall showed similar amounts of HE, NE, and normal tissue IPA (37.7 ± 13\%, 34.3 ± 14\%, and 28.0 ± 11\%, respectively; p = NS), registration of IPA injuries with 3moPA scarring demonstrated that 59.0 ± 19\% of scar resulted from NE tissue, 30.6 ± 15\% from HE tissue, and 10.4 ± 5\% from tissue identified as normal. Paired t-test comparisons were all statistically significant among NE, HE, and normal tissue types (p less than 0.001). Arrhythmia recurrence at 1-year follow-up correlated with the degree of wall enhancement 3moPA (p = 0.02).

Conclusion: Radiofrequency ablation results in heterogeneous injury on LGE MRI with both HE and NE wall lesions. The NE lesions demonstrate no-reflow characteristics and reveal a better predictor of final scar at 3 months. Scar correlates with procedure outcomes, further highlighting the importance of early scar prediction. (J Am Coll Cardiol 2011;58:177–85) © 2011 by the American College of Cardiology Foundation



D.J. Swenson, S.E. Geneser, J.G. Stinstra, R.M. Kirby, R.S. MacLeod. “Cardiac Position Sensitivity Study in the Electrocardiographic Forward Problem Using Stochastic Collocation and Boundary Element Methods,” In Annals of Biomedical Engineering, Vol. 39, No. 12, pp. 2900--2910. 2011.
DOI: 10.1007/s10439-011-0391-5
PubMed ID: 21909818
PubMed Central ID: PMC336204

ABSTRACT

The electrocardiogram (ECG) is ubiquitously employed as a diagnostic and monitoring tool for patients experiencing cardiac distress and/or disease. It is widely known that changes in heart position resulting from, for example, posture of the patient (sitting, standing, lying) and respiration significantly affect the body-surface potentials; however, few studies have quantitatively and systematically evaluated the effects of heart displacement on the ECG. The goal of this study was to evaluate the impact of positional changes of the heart on the ECG in the specific clinical setting of myocardial ischemia. To carry out the necessary comprehensive sensitivity analysis, we applied a relatively novel and highly efficient statistical approach, the generalized polynomial chaos-stochastic collocation method, to a boundary element formulation of the electrocardiographic forward problem, and we drove these simulations with measured epicardial potentials from whole-heart experiments. Results of the analysis identified regions on the body-surface where the potentials were especially sensitive to realistic heart motion. The standard deviation (STD) of ST-segment voltage changes caused by the apex of a normal heart, swinging forward and backward or side-to-side was approximately 0.2 mV. Variations were even larger, 0.3 mV, for a heart exhibiting elevated ischemic potentials. These variations could be large enough to mask or to mimic signs of ischemia in the ECG. Our results suggest possible modifications to ECG protocols that could reduce the diagnostic error related to postural changes in patients possibly suffering from myocardial ischemia.



J.D. Tate, J.G. Stinstra, T. Pilcher, A. Poursaid, E. Saarel, R.S. MacLeod. “Measuring Defibrillator Surface Potentials for Simulation Verification,” In Proceedings of the IEEE Engineering in Medicine and Biology Society EMBS 33rd Annual International Conference, pp. 239 - 242. 2011.
ISSN: 1557-170X
DOI: 10.1109/IEMBS.2011.6090045
PubMed ID: 22254294

ABSTRACT

Though implantable cardioverter defibrillators (ICDs) are increasing in use in both adults and children, little progress has been devoted to optimizing device and electrode placement. To facilitate effective ICD placement, especially in pediatric cases, we have developed a predictive model that evaluates the efficacy of a delivered shock. We have also developed an experimental validation approach based on measurements from clinical cases. The approach involves obtaining body surface potential maps of ICD discharges during implantation surgery using a limited lead selection and body surface estimation algorithm. Comparison of the simulated and measured potentials yielded very similar patterns and a typical correlation greater than 0.93, suggesting that the predictive simulation generates realistic potential values. This validation approach provides confidence in application of the simulation pipeline and offers areas to focus future improvements.

Keywords: Electric potential, Electric shock, Electrodes;Estimation, Lead;Surface reconstruction, Torso, Algorithms, Body Surface Potential Mapping, Computer Simulation, Defibrillators, Implantable, Humans, Models, Cardiovascular, Therapy, Computer-Assisted



J.D. Tate, J.G. Stinstra, T.A. Pilcher, R.S. MacLeod. “Measurement of Defibrillator Surface Potentials for Simulation Verification,” In Computing in Cardiology, In 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, IEEE, pp. 853--856. Aug, 2011.
DOI: 10.1109/iembs.2011.6090045



G.R. Vergara, S. Vijayakumar, E.G. Kholmovski, J.J. Blauer, M.A. Guttman, C. Gloschat, G. Payne, K. Vij, N.W. Akoum, M. Daccarett, C.J. McGann, R.S. Macleod, N.F. Marrouche. “Real-time magnetic resonance imaging-guided radiofrequency atrial ablation and visualization of lesion formation at 3 Tesla,” In Heart Rhythm, Vol. 8, No. 2, pp. 295--303. 2011.
PubMed ID: 21034854



D. Wang, R.M. Kirby, R.S. Macleod, C.R. Johnson. “An optimization framework for inversely estimating myocardial transmembrane potentials and localizing ischemia,” In Proceedings of the International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS), pp. 1680--1683. 2011.
DOI: 10.1109/IEMBS.2011.6090483
PubMed ID: 22254648
PubMed Central ID: PMC3336368

ABSTRACT

By combining a static bidomain heart model with a torso conduction model, we studied the inverse electrocardiographic problem of computing the transmembrane potentials (TMPs) throughout the myocardium from a body-surface potential map, and then used the recovered potentials to localize myocardial ischemia. Our main contribution is solving the inverse problem within a constrained optimization framework, which is a generalization of previous methods for calculating transmembrane potentials. The framework offers ample flexibility for users to apply various physiologically-based constraints, and is well supported by mature algorithms and solvers developed by the optimization community. By avoiding the traditional inverse ECG approach of building the lead-field matrix, the framework greatly reduces computation cost and, by setting the associated forward problem as a constraint, the framework enables one to flexibly set individualized resolutions for each physical variable, a desirable feature for balancing model accuracy, ill-conditioning and computation tractability. Although the task of computing myocardial TMPs at an arbitrary time instance remains an open problem, we showed that it is possible to obtain TMPs with moderate accuracy during the ST segment by assuming all cardiac cells are at the plateau phase. Moreover, the calculated TMPs yielded a good estimate of ischemic regions, which was of more clinical interest than the voltage values themselves. We conducted finite element simulations of a phantom experiment over a 2D torso model with synthetic ischemic data. Preliminary results indicated that our approach is feasible and suitably accurate for the common case of transmural myocardial ischemia.


2010


T.J. Badger, M. Daccarett, N.W. Akoum, Y.A. Adjei-Poku, N.S. Burgon, T.S. Haslam, S. Kalvaitis, S. Kuppahally, G. Vergara, L. McMullen, P.A. Anderson, E. Kholmovski, R.S. Macleod, N.F. Marrouche. “Evaluation of left atrial lesions after initial and repeat atrial fibrillation ablation: lessons learned from delayed-enhancement MRI in repeat ablation procedures,” In Circulation. Arrhythmia and Electrophysiology, Vol. 3, No. 3, pp. 249--259. 2010.
PubMed ID: 20335558



J.J.E. Blauer, J. Cates, C.J. McGann, E.G. Kholmovski, A. Alexander, M.W. Prastawa, S. Joshi, N.F. Marrouche, R.S. MacLeod. “MRI Based Injury Characterization Immediately Following Ablation of Atrial Fibrillation,” In Computing in Cardiology, Vol. 37, pp. 165--168. 2010.
ISSN: 0276−6574



B.M. Isaacson, J.G. Stinstra, R.S. MacLeod, P.F. Pasquina, R.D. Bloebaum. “Developing a Quantitative Measurement System for Assessing Heterotopic Ossification and Monitoring the Bioelectric Metrics from Electrically Induced Osseointegration in the Residual Limb of Service Members,” In Annals of Biomedical Engineering, Vol. 38, No. 9, pp. 2968-–2978. 2010.
PubMed ID: 20458630



M. Jolley, J. Stinstra, J. Tate, S. Pieper, R.S. Macleod, L. Chu, P. Wang, J.K. Triedman. “Finite element modeling of subcutaneous implantable defibrillator electrodes in an adult torso,” In Heart Rhythm, Vol. 7, No. 5, pp. 692--698. May, 2010.
DOI: 10.1016/j.hrthm.2010.01.030
PubMed ID: 20230927
PubMed Central ID: PMC3103844

ABSTRACT

BACKGROUND:
Total subcutaneous implantable subcutaneous defibrillators are in development, but optimal electrode configurations are not known.

OBJECTIVE:
We used image-based finite element models (FEM) to predict the myocardial electric field generated during defibrillation shocks (pseudo-DFT) in a wide variety of reported and innovative subcutaneous electrode positions to determine factors affecting optimal lead positions for subcutaneous implantable cardioverter-defibrillators (S-ICD).

METHODS:
An image-based FEM of an adult man was used to predict pseudo-DFTs across a wide range of technically feasible S-ICD electrode placements. Generator location, lead location, length, geometry and orientation, and spatial relation of electrodes to ventricular mass were systematically varied. Best electrode configurations were determined, and spatial factors contributing to low pseudo-DFTs were identified using regression and general linear models.

RESULTS:
A total of 122 single-electrode/array configurations and 28 dual-electrode configurations were simulated. Pseudo-DFTs for single-electrode orientations ranged from 0.60 to 16.0 (mean 2.65 +/- 2.48) times that predicted for the base case, an anterior-posterior configuration recently tested clinically. A total of 32 of 150 tested configurations (21%) had pseudo-DFT ratios /=1, indicating the possibility of multiple novel, efficient, and clinically relevant orientations. Favorable alignment of lead-generator vector with ventricular myocardium and increased lead length were the most important factors correlated with pseudo-DFT, accounting for 70% of the predicted variation (R(2) = 0.70, each factor P < .05) in a combined general linear modl in which parameter estimates were calculated for each factor.

CONCLUSION:
Further exploration of novel and efficient electrode configurations may be of value in the development of the S-ICD technologies and implant procedure. FEM modeling suggests that the choice of configurations that maximize shock vector alignment with the center of myocardial mass and use of longer leads is more likely to result in lower DFT.



S.S. Kuppahally, N. Akoum, N.S. Burgon, T.J. Badger, E.G. Kholmovski, S. Vijayakumar, S.N. Rao, J. Blauer, E.N. Fish, E.V. Dibella, R.S. Macleod, C. McGann, S.E. Litwin, N.F. Marrouche. “Left atrial strain and strain rate in patients with paroxysmal and persistent atrial fibrillation: relationship to left atrial structural remodeling detected by delayed-enhancement MRI,” In Circ Cardiovasc Imaging, Vol. 3, No. 3, pp. 231--239. 2010.
PubMed ID: 20133512