Migraine-Associated Common Genetic Variants Confer Greater Risk of Posterior vs. Anterior Circulation Ischemic Stroke☆.

OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.

Detailed phenotyping of posterior vs. anterior circulation ischemic stroke: a multi-center MRI study.

OBJECTIVE: Posterior circulation ischemic stroke (PCiS) constitutes 20-30% of ischemic stroke cases. Detailed information about differences between PCiS and anterior circulation ischemic stroke (ACiS) remains scarce. Such information might guide clinical decision making and prevention strategies. We studied risk factors and ischemic stroke subtypes in PCiS vs. ACiS and lesion location on magnetic resonance imaging (MRI) in PCiS. METHODS: Out of 3,301 MRIs from 12 sites in the National Institute of Neurological Disorders and Stroke (NINDS) Stroke Genetics Network (SiGN), we included 2,381 cases with acute DWI lesions. The definition of ACiS or PCiS was based on lesion location. We compared the groups using Chi-squared and logistic regression. RESULTS: PCiS occurred in 718 (30%) patients and ACiS in 1663 (70%). Diabetes and male sex were more common in PCiS vs. ACiS (diabetes 27% vs. 23%, p < 0.05; male sex 68% vs. 58%, p < 0.001). Both were independently associated with PCiS (diabetes, OR = 1.29; 95% CI 1.04-1.61; male sex, OR = 1.46; 95% CI 1.21-1.78). ACiS more commonly had large artery atherosclerosis (25% vs. 20%, p < 0.01) and cardioembolic mechanisms (17% vs. 11%, p < 0.001) compared to PCiS. Small artery occlusion was more common in PCiS vs. ACiS (20% vs. 14%, p < 0.001). Small artery occlusion accounted for 47% of solitary brainstem infarctions. CONCLUSION: Ischemic stroke subtypes differ between the two phenotypes. Diabetes and male sex have a stronger association with PCiS than ACiS. Definitive MRI-based PCiS diagnosis aids etiological investigation and contributes additional insights into specific risk factors and mechanisms of injury in PCiS.

Stopping Criteria for Log-Domain Diffeomorphic Demons Registration: An Experimental Survey for Radiotherapy Application.

A crucial issue in deformable image registration is achieving a robust registration algorithm at a reasonable computational cost. Given the iterative nature of the optimization procedure an algorithm must automatically detect convergence, and stop the iterative process when most appropriate. This paper ranks the performances of three stopping criteria and six stopping value computation strategies for a Log-Domain Demons Deformable registration method simulating both a coarse and a fine registration. The analyzed stopping criteria are: (a) velocity field update magnitude, (b) mean squared error, and (c) harmonic energy. Each stoping condition is formulated so that the user defines a threshold ∊, which quantifies the residual error that is acceptable for the particular problem and calculation strategy. In this work, we did not aim at assigning a value to e, but to give insights in how to evaluate and to set the threshold on a given exit strategy in a very popular registration scheme. Experiments on phantom and patient data demonstrate that comparing the optimization metric minimum over the most recent three iterations with the minimum over the fourth to sixth most recent iterations can be an appropriate algorithm stopping strategy. The harmonic energy was found to provide best trade-off between robustness and speed of convergence for the analyzed registration method at coarse registration, but was outperformed by mean squared error when all the original pixel information is used. This suggests the need of developing mathematically sound new convergence criteria in which both image and vector field information could be used to detect the actual convergence, which could be especially useful when considering multi-resolution registrations. Further work should be also dedicated to study same strategies performances in other deformable registration methods and body districts.

Keypoint Transfer Segmentation.

We present an image segmentation method that transfers label maps of entire organs from the training images to the novel image to be segmented. The transfer is based on sparse correspondences between keypoints that represent automatically identified distinctive image locations. Our segmentation algorithm consists of three steps: (i) keypoint matching, (ii) voting-based keypoint labeling, and (iii) keypoint-based probabilistic transfer of organ label maps. We introduce generative models for the inference of keypoint labels and for image segmentation, where keypoint matches are treated as a latent random variable and are marginalized out as part of the algorithm. We report segmentation results for abdominal organs in whole-body CT and in contrast-enhanced CT images. The accuracy of our method compares favorably to common multi-atlas segmentation while offering a speed-up of about three orders of magnitude. Furthermore, keypoint transfer requires no training phase or registration to an atlas. The algorithm's robustness enables the segmentation of scans with highly variable field-of-view.

SU-E-J-101: Weighted Voting Method for Multi-Atlas Segmentation in CT Scans.

PURPOSE: We investigate automating the task of segmenting structures in head and neck CT scans, to minimize time spent manually contouring. We focus on the brainstem and left and right parotids. METHODS: To generate contours for an unlabeled image, we assume an atlas of labeled images. We register each of these images to the unlabeled target image, transform their structures, and then use a weighted voting method for label fusion. Our registration method starts with multi-resolution translational alignment, then applies a relatively higher resolution affine alignment. We then employ a diffeomorphic demons registration to deform each atlas to the space of the targetimage. Our weighted voting method acts one structure at a time to determine for each voxel whether or not it exists in a structure. The weight for a voxel's vote from each atlas depends on the intensity difference of the target and the transformed atlas at that voxel, in addition to the distance of that voxel from the boundary of the structure. RESULTS: We applied our method to sixteen labeled images, generating automatic segmentations foreach using the other fifteen images as the atlas. We compared the resulting Dice and Hausdorff metrics with a majority voting method using the same registrations and saw remarkable improvement. Mean Dice scores were around .7, with maximum Hausdorff of about 15mm, and mean Hausdorffs around 2 or 3mm. CONCLUSIONS: Our method produces contours with boundaries usually only a few millimeters away from the manual contour, which could save physicians considerable time, because they only have to make small modifications to each slice instead of contouring from scratch.

WE-E-213CD-02: Gaussian Weighted Multi-Atlas Based Segmentation for Head and Neck Radiotherapy Planning.

PURPOSE: To develop a multi-atlas segmentation strategy for IMRT head and neck therapy planning. METHODS: The method was tested on thirty-one head and neck simulation CTs, without demographic or pathology pre-clustering. We compare Fixed Number (FN) and Thresholding (TH) selection (based on normalized mutual information ranking) of the atlases to be included for current patient segmentation. Next step is a pairwise demons Deformable Registration (DR) onto current patient CT. DR was extended to automatically compensate for patient different field of view. Propagated labels are combined according to a Gaussian Weighted (GW) fusion rule, adapted to poor soft tissues contrast. Agreement with manual segmentation was quantified in terms of Dice Similarity Coefficient (DSC). Selection methods, number of atlases used, as well as GW, average and majority voting fusion were discriminated by means of Friedman Test (a=5%). Experimental tuning of the algorithm parameters was performed on five patients, deriving an optimal configuration for each structure. RESULTS: DSC reduction was not significant when ten or more atlases are selected, whereas DSC for single most similar atlas selection is 10% lower in median. DSC of FN selection rule were significantly higher for most structures. Tubular structures may benefit from computing average contour rather than looking at the singular voxel contribution, whereas the best performing strategy for all other structures was GW. When half database is selected, final median DSC were 0.86, 0.80, 0.51, 0.81, 0.69 and 0.79 for mandible, spine, optical nerves, eyes, parotids and brainstem respectively. CONCLUSION: We developed an efficient algorithm for multiatlas based segmentation of planning CT volumes, based on DR and GW. FN selection of database atlases is foreseen to increase computational efficiency. The absence of clinical pre-clustering and specific imaging protocol on database subjects makes the results closer to real clinical application. "Progetto Roberto Rocca" funded by the Fondazione Fratelli Agostino and Enrico Rocca, Italy.

Ranking of stopping criteria for log domain diffeomorphic demons application in clinical radiation therapy.

Deformable Image Registration is a complex optimization algorithm with the goal of modeling a non-rigid transformation between two images. A crucial issue in this field is guaranteeing the user a robust but computationally reasonable algorithm. We rank the performances of four stopping criteria and six stopping value computation strategies for a log domain deformable registration. The stopping criteria we test are: (a) velocity field update magnitude, (b) vector field Jacobian, (c) mean squared error, and (d) harmonic energy. Experiments demonstrate that comparing the metric value over the last three iterations with the metric minimum of between four and six previous iterations is a robust and appropriate strategy. The harmonic energy and vector field update magnitude metrics give the best results in terms of robustness and speed of convergence.

Morphology-guided graph search for untangling objects: C. elegans analysis.

We present a novel approach for extracting cluttered objects based on their morphological properties. Specifically, we address the problem of untangling Caenorhabditis elegans clusters in high-throughput screening experiments. We represent the skeleton of each worm cluster by a sparse directed graph whose vertices and edges correspond to worm segments and their adjacencies, respectively. We then search for paths in the graph that are most likely to represent worms while minimizing overlap. The worm likelihood measure is defined on a low-dimensional feature space that captures different worm poses, obtained from a training set of isolated worms. We test the algorithm on 236 microscopy images, each containing 15 C. elegans worms, and demonstrate successful cluster untangling and high worm detection accuracy.

Prediction of Successful Memory Encoding from fMRI Data.

In this work, we explore the use of classification algorithms in predicting mental states from functional neuroimaging data. We train a linear support vector machine classifier to characterize spatial fMRI activation patterns. We employ a general linear model based feature extraction method and use the t-test for feature selection. We evaluate our method on a memory encoding task, using participants' subjective prediction about learning as a benchmark for our classifier. We show that the classifier achieves better than random predictions and the average accuracy is close to subject's own prediction performance. In addition, we validate our tool on a simple motor task where we demonstrate an average prediction accuracy of over 90%. Our experiments demonstrate that the classifier performance depends significantly on the complexity of the experimental design and the mental process of interest.

AnatomyBrowser: A novel approach to visualization and integration of medical information.

In this article, we present a novel technique for visualization of three-dimensional (3D) surface models, as well as its implementation in a system called AnatomyBrowser. Using our approach, visualization of 3D surface models is performed in two separate steps: a pre-rendering step, in which the models are rendered and saved in a special format, and an actual display step, in which the final result of rendering is generated using information from the prerendering step. Whereas prerendering requires high-end graphics hardware, the final image generation and display can be implemented efficiently in software. Moreover, our current implementation of AnatomyBrowser interface uses the Java programming language and can therefore be readily run on a wide range of systems, including low-end computers with no special graphics hardware. In addition to visualization of 3D models and 2D slices, AnatomyBrowser provides a rich set of annotation and cross-referencing capabilities. We demonstrate several possible applications for AnatomyBrowser, including interactive anatomy atlases, surgery planning, and assistance in segmentation.