Swetasudha Panda

Robust optic nerve segmentation on clinically acquired computed tomography.

Abstract. The optic nerve (ON) plays a critical role in many devastating pathological conditions. Segmentation of the ON has the ability to provide understanding of anatomical development and progression of diseases of the ON. Recently, methods have been proposed to segment the ON but progress toward full automation has been limited. We optimize registration and fusion methods for a new multi-atlas framework for automated segmentation of the ONs, eye globes, and muscles on clinically acquired computed tomography (CT) data. Briefly, the multi-atlas approach consists of determining a region of interest within each scan using affine registration, followed by nonrigid registration on reduced field of view atlases, and performing statistical fusion on the results. We evaluate the robustness of the approach by segmenting the ON structure in 501 clinically acquired CT scan volumes obtained from 183 subjects from a thyroid eye disease patient population. A subset of 30 scan volumes was manually labeled to assess accuracy and guide method choice. Of the 18 compared methods, the ANTS Symmetric Normalization registration and nonlocal spatial simultaneous truth and performance level estimation statistical fusion resulted in the best overall performance, resulting in a median Dice similarity coefficient of 0.77, which is comparable with inter-rater (human) reproducibility at 0.73.

Evaluation of multiatlas label fusion for in vivo magnetic resonance imaging orbital segmentation

Abstract. Multiatlas methods have been successful for brain segmentation, but their application to smaller anatomies remains relatively unexplored. We evaluate seven statistical and voting-based label fusion algorithms (and six additional variants) to segment the optic nerves, eye globes, and chiasm. For nonlocal simultaneous truth and performance level estimation (STAPLE), we evaluate different intensity similarity measures (including mean square difference, locally normalized cross-correlation, and a hybrid approach). Each algorithm is evaluated in terms of the Dice overlap and symmetric surface distance metrics. Finally, we evaluate refinement of label fusion results using a learning-based correction method for consistent bias correction and Markov random field regularization. The multiatlas labeling pipelines were evaluated on a cohort of 35 subjects including both healthy controls and patients. Across all three structures, nonlocal spatial STAPLE (NLSS) with a mixed weighting type provided the most consistent results; for the optic nerve NLSS resulted in a median Dice similarity coefficient of 0.81, mean surface distance of 0.41 mm, and Hausdorff distance 2.18 mm for the optic nerves. Joint label fusion resulted in slightly superior median performance for the optic nerves (0.82, 0.39 mm, and 2.15 mm), but slightly worse on the globes. The fully automated multiatlas labeling approach provides robust segmentations of orbital structures on magnetic resonance imaging even in patients for whom significant atrophy (optic nerve head drusen) or inflammation (multiple sclerosis) is present.

Shape-constrained multi-atlas segmentation of spleen in CT

Spleen segmentation on clinically acquired CT data is a challenging problem given the complicity and variability of abdominal anatomy. Multi-atlas segmentation is a potential method for robust estimation of spleen segmentations, but can be negatively impacted by registration errors. Although labeled atlases explicitly capture information related to feasible organ shapes, multi-atlas methods have largely used this information implicitly through registration. We propose to integrate a level set shape model into the traditional label fusion framework to create a shape-constrained multi-atlas segmentation framework. Briefly, we (1) adapt two alternative atlas-to-target registrations to obtain the loose bounds on the inner and outer boundaries of the spleen shape, (2) project the fusion estimate to registered shape models, and (3) convert the projected shape into shape priors. With the constraint of the shape prior, our proposed method offers a statistically significant improvement in spleen labeling accuracy with an increase in DSC by 0.06, a decrease in symmetric mean surface distance by 4.01 mm, and a decrease in symmetric Hausdorff surface distance by 23.21 mm when compared to a locally weighted vote (LWV) method.

Robust optic nerve segmentation on clinically acquired CT

The optic nerve is a sensitive central nervous system structure, which plays a critical role in many devastating pathological conditions. Several methods have been proposed in recent years to segment the optic nerve automatically, but progress toward full automation has been limited. Multi-atlas methods have been successful for brain segmentation, but their application to smaller anatomies remains relatively unexplored. Herein we evaluate a framework for robust and fully automated segmentation of the optic nerves, eye globes and muscles. We employ a robust registration procedure for accurate registrations, variable voxel resolution and image fieldof- view. We demonstrate the efficacy of an optimal combination of SyN registration and a recently proposed label fusion algorithm (Non-local Spatial STAPLE) that accounts for small-scale errors in registration correspondence. On a dataset containing 30 highly varying computed tomography (CT) images of the human brain, the optimal registration and label fusion pipeline resulted in a median Dice similarity coefficient of 0.77, symmetric mean surface distance error of 0.55 mm, symmetric Hausdorff distance error of 3.33 mm for the optic nerves. Simultaneously, we demonstrate the robustness of the optimal algorithm by segmenting the optic nerve structure in 316 CT scans obtained from 182 subjects from a thyroid eye disease (TED) patient population.

A brain MRI atlas of the common squirrel monkey, Saimiri sciureus

The common squirrel monkey, Saimiri sciureus, is a New World monkey with functional and microstructural organization of central nervous system similar to that of humans. It is one of the most commonly used South American primates in biomedical research. Unlike its Old World macaque cousins, no digital atlases have described the organization of the squirrel monkey brain. Here, we present a multi-modal magnetic resonance imaging (MRI) atlas constructed from the brain of an adult female squirrel monkey. In vivo MRI acquisitions include high resolution T2 structural imaging and low resolution diffusion tensor imaging. Ex vivo MRI acquisitions include high resolution T2 structural imaging and high resolution diffusion tensor imaging. Cortical regions were manually annotated on the co-registered volumes based on published histological sections.

Integrating linear optimization with structural modeling to increase HIV neutralization breadth

Computational protein design has been successful in modeling fixed backbone proteins in a single conformation. However, when modeling large ensembles of flexible proteins, current methods in protein design have been insufficient. Large barriers in the energy landscape are difficult to traverse while redesigning a protein sequence, and as a result current design methods only sample a fraction of available sequence space. We propose a new computational approach that combines traditional structure-based modeling using the Rosetta software suite with machine learning and integer linear programming to overcome limitations in the Rosetta sampling methods. We demonstrate the effectiveness of this method, which we call BROAD, by benchmarking the performance on increasing predicted breadth of anti-HIV antibodies. We use this novel method to increase predicted breadth of naturally-occurring antibody VRC23 against a panel of 180 divergent HIV viral strains and achieve 100% predicted binding against the panel. In addition, we compare the performance of this method to state-of-the-art multistate design in Rosetta and show that we can outperform the existing method significantly. We further demonstrate that sequences recovered by this method recover known binding motifs of broadly neutralizing anti-HIV antibodies. Finally, our approach is general and can be extended easily to other protein systems. Although our modeled antibodies were not tested in vitro, we predict that these variants would have greatly increased breadth compared to the wild-type antibody.

Scalable Initial State Interdiction for Factored MDPs

We propose a novel Stackelberg game model of MDP interdiction in which the defender modifies the initial state of the planner, who then responds by computing an optimal policy starting with that state. We first develop a novel approach for MDP interdiction in factored state space that allows the defender to modify the initial state. The resulting approach can be computationally expensive for large factored MDPs. To address this, we develop several interdiction algorithms that leverage variations of reinforcement learning using both linear and non-linear function approximation. Finally, we extend the interdiction framework to consider a Bayesian interdiction problem in which the interdictor is uncertain about some of the planners initial state features. Extensive experiments demonstrate the effectiveness of our approaches.