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

2017


J. Cates, L. Nevell, S. I. Prajapati, L. D. Nelon, J. Y. Chang, M. E. Randolph, B. Wood, C. Keller, R. T. Whitaker. “Shape analysis of the basioccipital bone in Pax7-deficient mice,” In Scientific Reports, Vol. 7, No. 1, Springer Nature, Dec, 2017.
DOI: 10.1038/s41598-017-18199-9

ABSTRACT

We compared the cranial base of newborn Pax7-deficient and wildtype mice using a computational shape modeling technology called particle-based modeling (PBM). We found systematic differences in the morphology of the basiooccipital bone, including a broadening of the basioccipital bone and an antero-inferior inflection of its posterior edge in the Pax7-deficient mice. We show that the Pax7 cell lineage contributes to the basioccipital bone and that the location of the Pax7 lineage correlates with the morphology most effected by Pax7 deficiency. Our results suggest that the Pax7-deficient mouse may be a suitable model for investigating the genetic control of the location and orientation of the foramen magnum, and changes in the breadth of the basioccipital.


2015


Y. Gao, L. Zhu, J. Cates, R. S. MacLeod, S. Bouix,, A. Tannenbaum. “A Kalman Filtering Perspective for Multiatlas Segmentation,” In SIAM J. Imaging Sciences, Vol. 8, No. 2, pp. 1007-1029. 2015.
DOI: 10.1137/130933423

ABSTRACT

In multiatlas segmentation, one typically registers several atlases to the novel image, and their respective segmented label images are transformed and fused to form the final segmentation. In this work, we provide a new dynamical system perspective for multiatlas segmentation, inspired by the following fact: The transformation that aligns the current atlas to the novel image can be not only computed by direct registration but also inferred from the transformation that aligns the previous atlas to the image together with the transformation between the two atlases. This process is similar to the global positioning system on a vehicle, which gets position by inquiring from the satellite and by employing the previous location and velocity—neither answer in isolation being perfect. To solve this problem, a dynamical system scheme is crucial to combine the two pieces of information; for example, a Kalman filtering scheme is used. Accordingly, in this work, a Kalman multiatlas segmentation is proposed to stabilize the global/affine registration step. The contributions of this work are twofold. First, it provides a new dynamical systematic perspective for standard independent multiatlas registrations, and it is solved by Kalman filtering. Second, with very little extra computation, it can be combined with most existing multiatlas segmentation schemes for better registration/segmentation accuracy.



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.


2014


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


2013


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

ABSTRACT

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



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

ABSTRACT

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



R. Karim, R.J. Housden, M. Balasubramaniam, Z. Chen, D. Perry, A. Uddin, Y. Al-Beyatti, E. Palkhi, P. Acheampong, S. Obom, A. Hennemuth, Y. Lu, W. Bai, W. Shi, Y. Gao, H.-O. Peitgen, P. Radau, R. Razavi, A. Tannenbaum, D. Rueckert, J. Cates, T. Schaeffter, D. Peters, R.S. MacLeod, K. Rhode. “Evaluation of Current Algorithms for Segmentation of Scar Tissue from Late Gadolinium Enhancement Cardiovascular Magnetic Resonance of the Left Atrium: An Open-Access Grand Challenge,” In Journal of Cardiovascular Magnetic Resonance, Vol. 15, No. 105, 2013.
DOI: 10.1186/1532-429X-15-105

ABSTRACT

Background: Late Gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging can be used to visualise regions of fibrosis and scarring in the left atrium (LA) myocardium. This can be important for treatment stratification of patients with atrial fibrillation (AF) and for assessment of treatment after radio frequency catheter ablation (RFCA). In this paper we present a standardised evaluation benchmarking framework for algorithms segmenting fibrosis and scar from LGE CMR images. The algorithms reported are the response to an open challenge that was put to the medical imaging community through an ISBI (IEEE International Symposium on Biomedical Imaging) workshop.

Methods: The image database consisted of 60 multicenter, multivendor LGE CMR image datasets from patients with AF, with 30 images taken before and 30 after RFCA for the treatment of AF. A reference standard for scar and fibrosis was established by merging manual segmentations from three observers. Furthermore, scar was also quantified using 2, 3 and 4 standard deviations (SD) and full-width-at-half-maximum (FWHM) methods. Seven institutions responded to the challenge: Imperial College (IC), Mevis Fraunhofer (MV), Sunnybrook Health Sciences (SY), Harvard/Boston University (HB), Yale School of Medicine (YL), King’s College London (KCL) and Utah CARMA (UTA, UTB). There were 8 different algorithms evaluated in this study.

Results: Some algorithms were able to perform significantly better than SD and FWHM methods in both pre- and post-ablation imaging. Segmentation in pre-ablation images was challenging and good correlation with the reference standard was found in post-ablation images. Overlap scores (out of 100) with the reference standard were as follows: Pre: IC = 37, MV = 22, SY = 17, YL = 48, KCL = 30, UTA = 42, UTB = 45; Post: IC = 76, MV = 85, SY = 73, HB = 76, YL = 84, KCL = 78, UTA = 78, UTB = 72.

Conclusions: The study concludes that currently no algorithm is deemed clearly better than others. There is scope for further algorithmic developments in LA fibrosis and scar quantification from LGE CMR images. Benchmarking of future scar segmentation algorithms is thus important. The proposed benchmarking framework is made available as open-source and new participants can evaluate their algorithms via a web-based interface.

Keywords: Late gadolinium enhancement, Cardiovascular magnetic resonance, Atrial fibrillation, Segmentation, Algorithm benchmarking



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

ABSTRACT

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

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

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


2012


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.
DOI: 10.1117/12.911228
PubMed ID: 24027625
PubMed Central ID: PMC3766973

ABSTRACT

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.
DOI: 10.1117/12.910833
PubMed ID: 24236224
PubMed Central ID: PMC3824273

ABSTRACT

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.



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.


2010


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


2009


M. Datar, J. Cates, P.T. Fletcher, S. Gouttard, G. Gerig, R.T. Whitaker. “Particle Based Shape Regression of Open Surfaces with Applications to Developmental Neuroimaging,” In Medical Image Computing and Computer-Assisted Intervention – MICCAI 2009, Lecture Notes in Computer Science LNCS, Vol. 5762, pp. 167--174. 2009.
DOI: 10.1007/978-3-642-04271-3_21
PubMed ID: 20426109



I. Oguz, M. Niethammer, J. Cates, R.T. Whitaker, P.T. Fletcher, C. Vachet, M. Styner. “Cortical Correspondence with Probabilistic Fiber Connectivity,” In Information Processing in Medical Imaging (IPMI), Lecture Notes in Computer Science (LCNS), Vol. 5636, pp. 651--663. 2009.
DOI: 10.1007/978-3-642-02498-6_54


2008


J. Cates, P.T. Fletcher, Z. Warnock, R.T. Whitaker. “A Shape Analysis Framework for Small Animal Phenotyping with Application to Mice with a Targeted Disruption of Hoxd11,” In Proceedings of the 5th IEEE International Symposium on Biomedical Imaging (ISBI '08), pp. 512--516. 2008.
DOI: 10.1109/ISBI.2008.4541045



J. Cates, P.T. Fletcher, M. Styner, H. Hazlett, R.T. Whitaker. “Particle-Based Shape Analysis of Multi-Object Complexes,” In Proceedings of the 11th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI '08), Lecture Notes In Computer Science (LCNS), pp. 477--485. 2008.
ISBN: 978-3-540-85987-1



I. Oguz, J. Cates, P.T. Fletcher, R.T. Whitaker, D. Cool, S. Aylward, M. Styner. “Cortical Correspondence using Entropy-Based Particle Systems and Local Features,” In 5th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, 2008. (ISBI 2008), pp. 1637--1640. 2008.


2007


J. Cates, P.T. Fletcher, M. Styner, M. Shenton, R.T. Whitaker. “Shape Modeling and Analysis with Entropy-Based Particle Systems,” In Proceedings of Information Processing in Medical Imaging (IPMI) 2007, LNCS 4584, pp. 333--345. 2007.


2006


J. Cates, M.D. Meyer, P.T. Fletcher, R.T. Witaker. “Entropy-Based Particle Systems for Shape Correspondence,” In Workshop on Mathematical Foundations of Computational Anatomy, MICCAI 2006, pp. 90--99. October, 2006.



J. Cates, D. Weinsten, M. Davis. “The Center for Integrative Biomedical Computing: Advancing Biomedical Science with Open Source,” In Proceedings of the IEEE International Symposium on Biomedical Imaging (ISBI) 2006, 2006.