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author:("Tu, showen")
1.  A classification approach to coreference in discharge summaries: 2011 i2b2 challenge 
Objective
To create a highly accurate coreference system in discharge summaries for the 2011 i2b2 challenge. The coreference categories include Person, Problem, Treatment, and Test.
Design
An integrated coreference resolution system was developed by exploiting Person attributes, contextual semantic clues, and world knowledge. It includes three subsystems: Person coreference system based on three Person attributes, Problem/Treatment/Test system based on numerous contextual semantic extractors and world knowledge, and Pronoun system based on a multi-class support vector machine classifier. The three Person attributes are patient, relative and hospital personnel. Contextual semantic extractors include anatomy, position, medication, indicator, temporal, spatial, section, modifier, equipment, operation, and assertion. The world knowledge is extracted from external resources such as Wikipedia.
Measurements
Micro-averaged precision, recall and F-measure in MUC, BCubed and CEAF were used to evaluate results.
Results
The system achieved an overall micro-averaged precision, recall and F-measure of 0.906, 0.925, and 0.915, respectively, on test data (from four hospitals) released by the challenge organizers. It achieved a precision, recall and F-measure of 0.905, 0.920 and 0.913, respectively, on test data without Pittsburgh data. We ranked the first out of 20 competing teams. Among the four sub-tasks on Person, Problem, Treatment, and Test, the highest F-measure was seen for Person coreference.
Conclusions
This system achieved encouraging results. The Person system can determine whether personal pronouns and proper names are coreferent or not. The Problem/Treatment/Test system benefits from both world knowledge in evaluating the similarity of two mentions and contextual semantic extractors in identifying semantic clues. The Pronoun system can automatically detect whether a Pronoun mention is coreferent to that of the other four types. This study demonstrates that it is feasible to accomplish the coreference task in discharge summaries.
doi:10.1136/amiajnl-2011-000734
PMCID: PMC3422828  PMID: 22505762
Natural language processing; information retrieval; clinical decision support; biomedical informatics; text processing; medical records
2.  Rotation-Invariant Features for Multi-Oriented Text Detection in Natural Images 
PLoS ONE  2013;8(8):e70173.
Texts in natural scenes carry rich semantic information, which can be used to assist a wide range of applications, such as object recognition, image/video retrieval, mapping/navigation, and human computer interaction. However, most existing systems are designed to detect and recognize horizontal (or near-horizontal) texts. Due to the increasing popularity of mobile-computing devices and applications, detecting texts of varying orientations from natural images under less controlled conditions has become an important but challenging task. In this paper, we propose a new algorithm to detect texts of varying orientations. Our algorithm is based on a two-level classification scheme and two sets of features specially designed for capturing the intrinsic characteristics of texts. To better evaluate the proposed method and compare it with the competing algorithms, we generate a comprehensive dataset with various types of texts in diverse real-world scenes. We also propose a new evaluation protocol, which is more suitable for benchmarking algorithms for detecting texts in varying orientations. Experiments on benchmark datasets demonstrate that our system compares favorably with the state-of-the-art algorithms when handling horizontal texts and achieves significantly enhanced performance on variant texts in complex natural scenes.
doi:10.1371/journal.pone.0070173
PMCID: PMC3734103  PMID: 23940544
3.  Automated hippocampal shape analysis predicts the onset of dementia in Mild Cognitive Impairment 
NeuroImage  2011;56(1):212-219.
The hippocampus is involved at the onset of the neuropathological pathways leading to Alzheimer’s disease (AD). Individuals with Mild Cognitive Impairment (MCI) are at increased risk of AD. Hippocampal volume has been shown to predict which MCI subjects will convert to AD. Our aim in the present study was to produce a fully automated prognostic procedure, scalable to high throughput clinical and research applications, for the prediction of MCI conversion to AD using 3D hippocampal morphology. We used an automated analysis for the extraction and mapping of the hippocampus from structural magnetic resonance scans to extract 3D hippocampal shape morphology, and we then applied machine learning classification to predict conversion from MCI to AD. We investigated the accuracy of prediction in 103 MCI subjects (mean age 74.1 years) from the longitudinal AddNeuroMed study. Our model correctly predicted MCI conversion to dementia within a year at an accuracy of 80% (sensitivity 77%, specificity 80%), a performance which is competitive with previous predictive models dependent on manual measurements. Categorization of MCI subjects based on hippocampal morphology revealed more rapid cognitive deterioration in MMSE scores (p < 0.01) and CERAD verbal memory (p < 0.01) in those subjects who were predicted to develop dementia relative to those predicted to remain stable. The pattern of atrophy associated with increased risk of conversion demonstrated initial degeneration in the anterior part of the cornus ammonis 1 (CA1) hippocampal subregion. We conclude that automated shape analysis generates sensitive measurements of early neurodegeneration which predates the onset of dementia and thus provides a prognostic biomarker for conversion of MCI to AD.
doi:10.1016/j.neuroimage.2011.01.050
PMCID: PMC3066277  PMID: 21272654
Neuroimaging; Hippocampus; Prognosis; Automated methods; Alzheimer’s disease; Mild Cognitive Impairment
4.  Lossless Online Ensemble Learning (LOEL) and Its Application to Subcortical Segmentation★ 
In this paper, we study the classification problem in the situation where large volumes of training data become available sequentially (online learning). In medical imaging, this is typical, e.g., a 3D brain MRI dataset may be gradually collected from a patient population, and not all of the data is available when the analysis begins. First, we describe two common ensemble learning algorithms, AdaBoost and bagging, and their corresponding online learning versions. We then show why each is ineffective for segmenting a gradually increasing set of medical images. Instead, we introduce a new ensemble learning algorithm, termed Lossless Online Ensemble Learning (LOEL). This algorithm is lossless in the online case, compared to its batch mode. LOEL outperformed online-AdaBoost and online-bagging when validated on a standardized dataset; it also performed better when used to segment the hippocampus from brain MRI scans of patients with Alzheimer’s Disease and matched healthy subjects. Among those tested, LOEL largely outperformed the alternative online learning algorithms and gave excellent error metrics that were consistent between the online and offline case; it also accurately distinguished AD subjects from healthy controls based on automated measures of hippocampal volume.
PMCID: PMC3148151  PMID: 20426141
5.  Comparison of AdaBoost and Support Vector Machines for Detecting Alzheimer’s Disease through Automated Hippocampal Segmentation 
We compared four automated methods for hippocampal segmentation using different machine learning algorithms (1) hierarchical AdaBoost, (2) Support Vector Machines (SVM) with manual feature selection, (3) hierarchical SVM with automated feature selection (Ada-SVM), and (4) a publicly available brain segmentation package (FreeSurfer). We trained our approaches using T1-weighted brain MRI’s from 30 subjects (10 normal elderly, 10 mild cognitive impairment (MCI), and 10 Alzheimer’s disease (AD)), and tested on an independent set of 40 subjects (20 normal, 20 AD). Manually segmented gold standard hippocampal tracings were available for all subjects (training and testing). We assessed each approach’s accuracy relative to manual segmentations, and its power to map AD effects. We then converted the segmentations into parametric surfaces to map disease effects on anatomy. After surface reconstruction, we computed significance maps, and overall corrected p-values, for the 3D profile of shape differences between AD and normal subjects. Our AdaBoost and Ada-SVM segmentations compared favorably with the manual segmentations and detected disease effects as well as FreeSurfer on the data tested. Cumulative p-value plots, in conjunction with the False Discovery Rate method, were used to examine the power of each method to detect correlations with diagnosis and cognitive scores. We also evaluated how segmentation accuracy depended on the size of the training set, providing practical information for future users of this technique.
doi:10.1109/TMI.2009.2021941
PMCID: PMC2805054  PMID: 19457748
AdaBoost; Alzheimer’s disease; hippocampal segmentation; support vector machines; surface modeling; Subcoritcal Segmentation; Hippocampus
6.  Automated 3D Mapping of Hippocampal Atrophy and its Clinical Correlates in 400 Subjects with Alzheimer’s Disease, Mild Cognitive Impairment, and Elderly Controls 
Human brain mapping  2009;30(9):2766-2788.
We used a new method we developed for automated hippocampal segmentation, called the auto context model (ACM), to analyze brain MRI scans of 400 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). After training the classifier on 21 hand-labeled expert segmentations, we created binary maps of the hippocampus for three age- and sex-matched groups: 100 subjects with Alzheimer’s disease (AD), 200 with mild cognitive impairment (MCI) and 100 elderly controls (mean age: 75.84; SD: 6.64). Hippocampal traces were converted to parametric surface meshes and a radial atrophy mapping technique was used to compute average surface models and local statistics of atrophy. Surface-based statistical maps visualized links between regional atrophy and diagnosis (MCI versus controls: p = 0.008; MCI versus AD: p = 0.001), mini-mental state exam (MMSE) scores, and global and sum-of-boxes clinical dementia rating scores (CDR; all p < 0.0001, corrected). Right but not left hippocampal atrophy was associated with geriatric depression scores (p = 0.004, corrected); hippocampal atrophy was not associated with subsequent decline in MMSE and CDR scores, educational level, ApoE genotype, systolic or diastolic blood pressure measures, or homocysteine. We gradually reduced sample sizes and used false discovery rate curves to examine the method’s power to detect associations with diagnosis and cognition in smaller samples. 40 subjects were sufficient to discriminate AD from normal and correlate atrophy with CDR scores; 104, 200 and 304 subjects, respectively, were required to correlate MMSE with atrophy, to distinguish MCI from normal, and MCI from AD.
doi:10.1002/hbm.20708
PMCID: PMC2733926  PMID: 19172649
7.  Joint Sulcal Detection on Cortical Surfaces With Graphical Models and Boosted Priors 
In this paper, we propose an automated approach for the joint detection of major sulci on cortical surfaces. By representing sulci as nodes in a graphical model, we incorporate Markovian relations between sulci and formulate their detection as a maximum a posteriori (MAP) estimation problem over the joint space of major sulci. To make the inference tractable, a sample space with a finite number of candidate curves is automatically generated at each node based on the Hamilton–Jacobi skeleton of sulcal regions. Using the AdaBoost algorithm, we learn both individual and pairwise shape priors of sulcal curves from training data, which are then used to define potential functions in the graphical model based on the connection between AdaBoost and logistic regression. Finally belief propagation is used to perform the MAP inference and select the joint detection results from the sample spaces of candidate curves. In our experiments, we quantitatively validate our algorithm with manually traced curves and demonstrate the automatically detected curves can capture the main body of sulci very accurately. A comparison with independently detected results is also conducted to illustrate the advantage of the joint detection approach.
doi:10.1109/TMI.2008.2004402
PMCID: PMC2754577  PMID: 19244008
Index Terms; AdaBoost; boosted prior; cortex; graphical model; major sulci; shape prior
8.  Brain Anatomical Structure Segmentation by Hybrid Discriminative/Generative Models 
In this paper, a hybrid discriminative/generative model for brain anatomical structure segmentation is proposed. The learning aspect of the approach is emphasized. In the discriminative appearance models, various cues such as intensity and curvatures are combined to locally capture the complex appearances of different anatomical structures. A probabilistic boosting tree (PBT) framework is adopted to learn multi-class discriminative models that combine hundreds of features across different scales. On the generative model side, both global and local shape models are used to capture the shape information about each anatomical structure. The parameters to combine the discriminative appearance and generative shape models are also automatically learned. Thus low-level and high-level information is learned and integrated in a hybrid model. Segmentations are obtained by minimizing an energy function associated with the proposed hybrid model. Finally, a grid-face structure is designed to explicitly represent the 3D region topology. This representation handles an arbitrary number of regions and facilitates fast surface evolution. Our system was trained and tested on a set of 3D MRI volumes and the results obtained are encouraging.
doi:10.1109/TMI.2007.908121
PMCID: PMC2807446  PMID: 18390346
Brain anatomical structures; segmentation; probabilistic boosting tree; discriminative models; generative models
9.  Validation of a Fully Automated 3D Hippocampal Segmentation Method Using Subjects with Alzheimer's Disease, Mild Cognitive Impairment, and Elderly Controls 
NeuroImage  2008;43(1):59-68.
We introduce a new method for brain MRI segmentation, called the auto context model (ACM), to segment the hippocampus automatically in 3D T1-weighted structural brain MRI scans of subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). In a training phase, our algorithm used 21 hand-labeled segmentations to learn a classification rule for hippocampal versus non-hippocampal regions using a modified AdaBoost method, based on ∼18,000 features (image intensity, position, image curvatures, image gradients, tissue classification maps of gray/white matter and CSF, and mean, standard deviation, and Haar filters of size 1×1×1 to 7×7×7). We linearly registered all brains to a standard template to devise a basic shape prior to capture the global shape of the hippocampus, defined as the pointwise summation of all the training masks. We also included curvature, gradient, mean, standard deviation, and Haar filters of the shape prior and the tissue classified images as features. During each iteration of ACM - our extension of AdaBoost - the Bayesian posterior distribution of the labeling was fed back in as an input, along with its neighborhood features, as new features for AdaBoost to use. In validation studies, we compared our results with hand-labeled segmentations by two experts. Using a leave-one-out approach and standard overlap and distance error metrics, our automated segmentations agreed well with human raters; any differences were comparable to differences between trained human raters. Our error metrics compare favorably with those previously reported for other automated hippocampal segmentations, suggesting the utility of the approach for large-scale studies.
doi:10.1016/j.neuroimage.2008.07.003
PMCID: PMC2624575  PMID: 18675918
10.  Identifying Heritable Brain Phenotypes in an Extended Pedigree of Vervet Monkeys 
The area and volume of brain structural features, as assessed by high-resolution 3D magnetic resonance imaging (MRI), are among the most heritable measures relating to the human central nervous system. We have conducted MRI scanning of all available monkeys over 2 years of age (n=357) from the extended multigenerational pedigree of the Vervet Research Colony (VRC). Using a combination of automated and manual segmentation we have quantified several correlated but distinct brain structural phenotypes. The estimated heritabilities (h2) for these measures in the VRC are higher than those reported previously for such features in humans or in other non human primates (NHP): total brain volume (h2=0.99, standard error (se)=0.06), cerebral volume (h2=0.98, se=0.06), cerebellar volume (h2=0.86, se=0.09), hippocampal volume (h2=0.95, se=0.07) and corpus callosum cross-sectional areas (h2=0.87, se=0.07). These findings indicate that, in the controlled environment and with the inbreeding structure of the VRC, additive genetic factors account for almost all of the observed variance in brain structure, and suggest the potential of the VRC for genetic mapping of quantitative trait loci (QTL) underlying such variance.
doi:10.1523/JNEUROSCI.5153-08.2009
PMCID: PMC2716293  PMID: 19261882
Genetics; Primate; Imaging; Hippocampus; Cerebellum; Callosum
11.  Automated mapping of hippocampal atrophy in 1-year repeat MRI data from 490 subjects with Alzheimer’s disease, mild cognitive impairment, and elderly controls 
NeuroImage  2008;45(1 Suppl):S3-15.
As one of the earliest structures to degenerate in Alzheimer’s disease (AD), the hippocampus is the target of many studies of factors that influence rates of brain degeneration in the elderly. In one of the largest brain mapping studies to date, we mapped the 3D profile of hippocampal degeneration over time in 490 subjects scanned twice with brain MRI over a 1-year interval (980 scans). We examined baseline and 1-year follow-up scans of 97 AD subjects (49 males/48 females), 148 healthy control subjects (75 males/73 females), and 245 subjects with mild cognitive impairment (MCI; 160 males/85 females). We used our previously validated automated segmentation method, based on AdaBoost, to create 3D hippocampal surface models in all 980 scans. Hippocampal volume loss rates increased with worsening diagnosis (normal=0.66%/year; MCI=3.12%/year; AD=5.59%/year), and correlated with both baseline and interval changes in Mini-Mental State Examination (MMSE) scores and global and sum-of-boxes Clinical Dementia Rating scale (CDR) scores. Surface-based statistical maps visualized a selective profile of ongoing atrophy in all three diagnostic groups. Healthy controls carrying the ApoE4 gene atrophied faster than non-carriers, while more educated controls atrophied more slowly; converters from MCI to AD showed faster atrophy than non-converters. Hippocampal loss rates can be rapidly mapped, and they track cognitive decline closely enough to be used as surrogate markers of Alzheimer’s disease in drug trials. They also reveal genetically greater atrophy in cognitively intact subjects.
doi:10.1016/j.neuroimage.2008.10.043
PMCID: PMC2733354  PMID: 19041724
12.  Direct Mapping of Hippocampal Surfaces with Intrinsic Shape Context 
NeuroImage  2007;37(3):792-807.
We propose in this paper a new method for the mapping of hippocampal (HC) surfaces to establish correspondences between points on HC surfaces and enable localized HC shape analysis. A novel geometric feature, the intrinsic shape context, is defined to capture the global characteristics of the HC shapes. Based on this intrinsic feature, an automatic algorithm is developed to detect a set of landmark curves that are stable across population. The direct map between a source and target HC surface is then solved as the minimizer of a harmonic energy function defined on the source surface with landmark constraints. For numerical solutions, we compute the map with the approach of solving partial differential equations on implicit surfaces. The direct mapping method has the following properties: 1) it has the advantage of being automatic; 2) it is invariant to the pose of HC shapes. In our experiments, we apply the direct mapping method to study temporal changes of HC asymmetry in Alzheimer disease (AD) using HC surfaces from 12 AD patients and 14 normal controls. Our results show that the AD group has a different trend in temporal changes of HC asymmetry than the group of normal controls. We also demonstrate the flexibility of the direct mapping method by applying it to construct spherical maps of HC surfaces. Spherical harmonics (SPHARM) analysis is then applied and it confirms our results about temporal changes of HC asymmetry in AD.
doi:10.1016/j.neuroimage.2007.05.016
PMCID: PMC2227952  PMID: 17625918
Hippocampal surface; intrinsic shape context; direct mapping; shape analysis; implicit representation; level set; temporal changes; asymmetry; Alzheimer disease

Results 1-12 (12)