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At least 379 records · Page 21

Computer-aided diagnosis for classifying benign versus malignant thyroid nodules based on ultrasound images: A comparison with radiologist-based assessments

Purpose: To develop a semiautomated computer-aided diagnosis (CAD) system for thyroid cancer using two-dimensional ultrasound images that can be used to yield a second opinion in the clinic to differentiate malignant and benign lesions. Methods: A total of 118 ultrasound images that included axial and longitudinal images from patients with biopsy-confirmed malignant (n = 30) and benign (n = 29) nodules were collected. Thyroid CAD software was developed to extract quantitative features from these images based on thyroid nodule segmentation in which adaptive diffusion flow for active contours was used. Various features, including histogram, intensity differences, elliptical fit, gray-level co-occurrence matrixes, and gray-level run-length matrixes, were evaluated for each region imaged. Based on these imaging features, a support vector machine (SVM) classifier was used to differentiate benign and malignant nodules. Leave-one-out cross-validation with sequential forward feature selection was performed to evaluate the overall accuracy of this method. Additionally, analyses with contingency tables and receiver operating characteristic (ROC) curves were performed to compare the performance of CAD with visual inspection by expert radiologists based on established gold standards. Results: Most univariate features for this proposed CAD system attained accuracies that ranged from 78.0% to 83.1%. When optimal SVM parameters that were established using a grid search method with features that radiologists use for visual inspection were employed, the authors could attain rates of accuracy that ranged from 72.9% to 84.7%. Using leave-one-out cross-validation results in a multivariate analysis of various features, the highest accuracy achieved using the proposed CAD system was 98.3%, whereas visual inspection by radiologists reached 94.9% accuracy. To obtain the highest accuracies, “axial ratio” and “max probability” in axial images were most frequently included in the optimal feature sets for the authors’ proposed CAD system, while “shape” and “calcification” in longitudinal images were most frequently included in the optimal feature sets for visual inspection by radiologists. The computed areas under curves in the ROC analysis were 0.986 and 0.979 for the proposed CAD system and visual inspection by radiologists, respectively; no significant difference was detected between these groups. Conclusions: The use of thyroid CAD to differentiate malignant from benign lesions shows accuracy similar to that obtained via visual inspection by radiologists. Thyroid CAD might be considered a viable way to generate a second opinion for radiologists in clinical practice.

61 RADIATION PROTECTION AND DOSIMETRY↗

Automatic coronary calcium scoring using noncontrast and contrast CT images

Purpose: Calcium scoring is widely used to assess the risk of coronary heart disease (CHD). Accurate coronary artery calcification detection in noncontrast CT image is a prerequisite step for coronary calcium scoring. Currently, calcified lesions in the coronary arteries are manually identified by radiologists in clinical practice. Thus, in this paper, a fully automatic calcium scoring method was developed to alleviate the work load of the radiologists or cardiologists. Methods: The challenge of automatic coronary calcification detection is to discriminate the calcification in the coronary arteries from the calcification in the other tissues. Since the anatomy of coronary arteries is difficult to be observed in the noncontrast CT images, the contrast CT image of the same patient is used to extract the regions of the aorta, heart, and coronary arteries. Then, a patient-specific region-of-interest (ROI) is generated in the noncontrast CT image according to the segmentation results in the contrast CT image. This patient-specific ROI focuses on the regions in the neighborhood of coronary arteries for calcification detection, which can eliminate the calcifications in the surrounding tissues. A support vector machine classifier is applied finally to refine the results by removing possible image noise. Furthermore, the calcified lesions in the noncontrast images belonging to the different main coronary arteries are identified automatically using the labeling results of the extracted coronary arteries. Results: Forty datasets from four different CT machine vendors were used to evaluate their algorithm, which were provided by the MICCAI 2014 Coronary Calcium Scoring (orCaScore) Challenge. The sensitivity and positive predictive value for the volume of detected calcifications are 0.989 and 0.948. Only one patient out of 40 patients had been assigned to the wrong risk category defined according to Agatston scores (0, 1–100, 101–300, >300) by comparing with the ground truth. Conclusions: The calcified lesions in the noncontrast CT images can be detected automatically by using the segmentation results of the aorta, heart, and coronary arteries obtained in the contrast CT images with a very high accuracy.

60 APPLIED LIFE SCIENCES↗

Automated detection of pulmonary nodules in PET/CT images: Ensemble false-positive reduction using a convolutional neural network technique

Purpose: Automated detection of solitary pulmonary nodules using positron emission tomography (PET) and computed tomography (CT) images shows good sensitivity; however, it is difficult to detect nodules in contact with normal organs, and additional efforts are needed so that the number of false positives (FPs) can be further reduced. In this paper, the authors propose an improved FP-reduction method for the detection of pulmonary nodules in PET/CT images by means of convolutional neural networks (CNNs). Methods: The overall scheme detects pulmonary nodules using both CT and PET images. In the CT images, a massive region is first detected using an active contour filter, which is a type of contrast enhancement filter that has a deformable kernel shape. Subsequently, high-uptake regions detected by the PET images are merged with the regions detected by the CT images. FP candidates are eliminated using an ensemble method; it consists of two feature extractions, one by shape/metabolic feature analysis and the other by a CNN, followed by a two-step classifier, one step being rule based and the other being based on support vector machines. Results: The authors evaluated the detection performance using 104 PET/CT images collected by a cancer-screening program. The sensitivity in detecting candidates at an initial stage was 97.2%, with 72.8 FPs/case. After performing the proposed FP-reduction method, the sensitivity of detection was 90.1%, with 4.9 FPs/case; the proposed method eliminated approximately half the FPs existing in the previous study. Conclusions: An improved FP-reduction scheme using CNN technique has been developed for the detection of pulmonary nodules in PET/CT images. The authors’ ensemble FP-reduction method eliminated 93% of the FPs; their proposed method using CNN technique eliminates approximately half the FPs existing in the previous study. These results indicate that their method may be useful in the computer-aided detection of pulmonary nodules using PET/CT images.

60 APPLIED LIFE SCIENCES↗

MRI texture features as biomarkers to predict MGMT methylation status in glioblastomas

Purpose: Imaging biomarker research focuses on discovering relationships between radiological features and histological findings. In glioblastoma patients, methylation of the O{sup 6}-methylguanine methyltransferase (MGMT) gene promoter is positively correlated with an increased effectiveness of current standard of care. In this paper, the authors investigate texture features as potential imaging biomarkers for capturing the MGMT methylation status of glioblastoma multiforme (GBM) tumors when combined with supervised classification schemes. Methods: A retrospective study of 155 GBM patients with known MGMT methylation status was conducted. Co-occurrence and run length texture features were calculated, and both support vector machines (SVMs) and random forest classifiers were used to predict MGMT methylation status. Results: The best classification system (an SVM-based classifier) had a maximum area under the receiver-operating characteristic (ROC) curve of 0.85 (95% CI: 0.78–0.91) using four texture features (correlation, energy, entropy, and local intensity) originating from the T2-weighted images, yielding at the optimal threshold of the ROC curve, a sensitivity of 0.803 and a specificity of 0.813. Conclusions: Results show that supervised machine learning of MRI texture features can predict MGMT methylation status in preoperative GBM tumors, thus providing a new noninvasive imaging biomarker.

60 APPLIED LIFE SCIENCES↗

Mediastinal lymph node detection and station mapping on chest CT using spatial priors and random forest

Purpose: To develop an automated system for mediastinal lymph node detection and station mapping for chest CT. Methods: The contextual organs, trachea, lungs, and spine are first automatically identified to locate the region of interest (ROI) (mediastinum). The authors employ shape features derived from Hessian analysis, local object scale, and circular transformation that are computed per voxel in the ROI. Eight more anatomical structures are simultaneously segmented by multiatlas label fusion. Spatial priors are defined as the relative multidimensional distance vectors corresponding to each structure. Intensity, shape, and spatial prior features are integrated and parsed by a random forest classifier for lymph node detection. The detected candidates are then segmented by the following curve evolution process. Texture features are computed on the segmented lymph nodes and a support vector machine committee is used for final classification. For lymph node station labeling, based on the segmentation results of the above anatomical structures, the textual definitions of mediastinal lymph node map according to the International Association for the Study of Lung Cancer are converted into patient-specific color-coded CT image, where the lymph node station can be automatically assigned for each detected node. Results: The chest CT volumes from 70 patients with 316 enlarged mediastinal lymph nodes are used for validation. For lymph node detection, their system achieves 88% sensitivity at eight false positives per patient. For lymph node station labeling, 84.5% of lymph nodes are correctly assigned to their stations. Conclusions: Multiple-channel shape, intensity, and spatial prior features aggregated by a random forest classifier improve mediastinal lymph node detection on chest CT. Using the location information of segmented anatomic structures from the multiatlas formulation enables accurate identification of lymph node stations.

60 APPLIED LIFE SCIENCES↗

SU-F-R-46: Predicting Distant Failure in Lung SBRT Using Multi-Objective Radiomics Model

Purpose: To predict distant failure in lung stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer (NSCLC) by using a new multi-objective radiomics model. Methods: Currently, most available radiomics models use the overall accuracy as the objective function. However, due to data imbalance, a single object may not reflect the performance of a predictive model. Therefore, we developed a multi-objective radiomics model which considers both sensitivity and specificity as the objective functions simultaneously. The new model is used to predict distant failure in lung SBRT using 52 patients treated at our institute. Quantitative imaging features of PET and CT as well as clinical parameters are utilized to build the predictive model. Image features include intensity features (9), textural features (12) and geometric features (8). Clinical parameters for each patient include demographic parameters (4), tumor characteristics (8), treatment faction schemes (4) and pretreatment medicines (6). The modelling procedure consists of two steps: extracting features from segmented tumors in PET and CT; and selecting features and training model parameters based on multi-objective. Support Vector Machine (SVM) is used as the predictive model, while a nondominated sorting-based multi-objective evolutionary computation algorithm II (NSGA-II) is used for solving the multi-objective optimization. Results: The accuracy for PET, clinical, CT, PET+clinical, PET+CT, CT+clinical, PET+CT+clinical are 71.15%, 84.62%, 84.62%, 85.54%, 82.69%, 84.62%, 86.54%, respectively. The sensitivities for the above seven combinations are 41.76%, 58.33%, 50.00%, 50.00%, 41.67%, 41.67%, 58.33%, while the specificities are 80.00%, 92.50%, 90.00%, 97.50%, 92.50%, 97.50%, 97.50%. Conclusion: A new multi-objective radiomics model for predicting distant failure in NSCLC treated with SBRT was developed. The experimental results show that the best performance can be obtained by combining all features.

60 APPLIED LIFE SCIENCES↗

SU-G-BRC-13: Model Based Classification for Optimal Position Selection for Left-Sided Breast Radiotherapy: Free Breathing, DIBH, Or Prone

Purpose: There are clinical decision challenges to select optimal treatment positions for left-sided breast cancer patients—supine free breathing (FB), supine Deep Inspiration Breath Hold (DIBH) and prone free breathing (prone). Physicians often make the decision based on experiences and trials, which might not always result optimal OAR doses. We herein propose a mathematical model to predict the lowest OAR doses among these three positions, providing a quantitative tool for corresponding clinical decision. Methods: Patients were scanned in FB, DIBH, and prone positions under an IRB approved protocol. Tangential beam plans were generated for each position, and OAR doses were calculated. The position with least OAR doses is defined as the optimal position. The following features were extracted from each scan to build the model: heart, ipsilateral lung, breast volume, in-field heart, ipsilateral lung volume, distance between heart and target, laterality of heart, and dose to heart and ipsilateral lung. Principal Components Analysis (PCA) was applied to remove the co-linearity of the input data and also to lower the data dimensionality. Feature selection, another method to reduce dimensionality, was applied as a comparison. Support Vector Machine (SVM) was then used for classification. Thirtyseven patient data were acquired; up to now, five patient plans were available. K-fold cross validation was used to validate the accuracy of the classifier model with small training size. Results: The classification results and K-fold cross validation demonstrated the model is capable of predicting the optimal position for patients. The accuracy of K-fold cross validations has reached 80%. Compared to PCA, feature selection allows causal features of dose to be determined. This provides more clinical insights. Conclusion: The proposed classification system appeared to be feasible. We are generating plans for the rest of the 37 patient images, and more statistically significant results are to be presented.

60 APPLIED LIFE SCIENCES↗

SU-G-BRA-09: Estimation of Motion Tracking Uncertainty for Real-Time Adaptive Imaging

Purpose: kV fluoroscopic imaging combined with MV treatment beam imaging has been investigated for intrafractional motion monitoring and correction. It is, however, subject to additional kV imaging dose to normal tissue. To balance tracking accuracy and imaging dose, we previously proposed an adaptive imaging strategy to dynamically decide future imaging type and moments based on motion tracking uncertainty. kV imaging may be used continuously for maximal accuracy or only when the position uncertainty (probability of out of threshold) is high if a preset imaging dose limit is considered. In this work, we propose more accurate methods to estimate tracking uncertainty through analyzing acquired data in real-time. Methods: We simulated motion tracking process based on a previously developed imaging framework (MV + initial seconds of kV imaging) using real-time breathing data from 42 patients. Motion tracking errors for each time point were collected together with the time point’s corresponding features, such as tumor motion speed and 2D tracking error of previous time points, etc. We tested three methods for error uncertainty estimation based on the features: conditional probability distribution, logistic regression modeling, and support vector machine (SVM) classification to detect errors exceeding a threshold. Results: For conditional probability distribution, polynomial regressions on three features (previous tracking error, prediction quality, and cosine of the angle between the trajectory and the treatment beam) showed strong correlation with the variation (uncertainty) of the mean 3D tracking error and its standard deviation: R-square = 0.94 and 0.90, respectively. The logistic regression and SVM classification successfully identified about 95% of tracking errors exceeding 2.5mm threshold. Conclusion: The proposed methods can reliably estimate the motion tracking uncertainty in real-time, which can be used to guide adaptive additional imaging to confirm the tumor is within the margin or initialize motion compensation if it is out of the margin.

60 APPLIED LIFE SCIENCES↗

MO-DE-207B-05: Predicting Gene Mutations in Renal Cell Carcinoma Based On CT Imaging Features: Validation Using TCGA-TCIA Datasets

Purpose: The goal of this work is to investigate the use of contrast enhanced computed tomographic (CT) features for the prediction of mutations of BAP1, PBRM1, and VHL genes in renal cell carcinoma (RCC). Methods: For this study, we used two patient databases with renal cell carcinoma (RCC). The first one consisted of 33 patients from our institution (UT Southwestern Medical Center, UTSW). The second one consisted of 24 patients from the Cancer Imaging Archive (TCIA), where each patient is connected by a unique identi?er to the tissue samples from the Cancer Genome Atlas (TCGA). From the contrast enhanced CT image of each patient, tumor contour was first delineated by a physician. Geometry, intensity, and texture features were extracted from the delineated tumor. Based on UTSW dataset, we completed feature selection and trained a support vector machine (SVM) classifier to predict mutations of BAP1, PBRM1 and VHL genes. We then used TCIA-TCGA dataset to validate the predictive model build upon UTSW dataset. Results: The prediction accuracy of gene expression of TCIA-TCGA patients was 0.83 (20 of 24), 0.83 (20 of 24), and 0.75 (18 of 24) for BAP1, PBRM1, and VHL respectively. For BAP1 gene, texture feature was the most prominent feature type. For PBRM1 gene, intensity feature was the most prominent. For VHL gene, geometry, intensity, and texture features were all important. Conclusion: Using our feature selection strategy and models, we achieved predictive accuracy over 0.75 for all three genes under the condition of using patient data from one institution for training and data from other institutions for testing. These results suggest that radiogenomics can be used to aid in prognosis and used as convenient surrogates for expensive and time consuming gene assay procedures.

60 APPLIED LIFE SCIENCES↗

TU-D-207B-01: A Prediction Model for Distinguishing Radiation Necrosis From Tumor Progression After Gamma Knife Radiosurgery Based On Radiomics Features From MR Images

Purpose: To develop and validate a prediction model using radiomics features extracted from MR images to distinguish radiation necrosis from tumor progression for brain metastases treated with Gamma knife radiosurgery. Methods: The images used to develop the model were T1 post-contrast MR scans from 71 patients who had had pathologic confirmation of necrosis or progression; 1 lesion was identified per patient (17 necrosis and 54 progression). Radiomics features were extracted from 2 images at 2 time points per patient, both obtained prior to resection. Each lesion was manually contoured on each image, and 282 radiomics features were calculated for each lesion. The correlation for each radiomics feature between two time points was calculated within each group to identify a subset of features with distinct values between two groups. The delta of this subset of radiomics features, characterizing changes from the earlier time to the later one, was included as a covariate to build a prediction model using support vector machines with a cubic polynomial kernel function. The model was evaluated with a 10-fold cross-validation. Results: Forty radiomics features were selected based on consistent correlation values of approximately 0 for the necrosis group and >0.2 for the progression group. In performing the 10-fold cross-validation, we narrowed this number down to 11 delta radiomics features for the model. This 11-delta-feature model showed an overall prediction accuracy of 83.1%, with a true positive rate of 58.8% in predicting necrosis and 90.7% for predicting tumor progression. The area under the curve for the prediction model was 0.79. Conclusion: These delta radiomics features extracted from MR scans showed potential for distinguishing radiation necrosis from tumor progression. This tool may be a useful, noninvasive means of determining the status of an enlarging lesion after radiosurgery, aiding decision-making regarding surgical resection versus conservative medical management.

60 APPLIED LIFE SCIENCES↗

3D exemplar-based random walks for tooth segmentation from cone-beam computed tomography images

Purpose: Tooth segmentation is an essential step in acquiring patient-specific dental geometries from cone-beam computed tomography (CBCT) images. Tooth segmentation from CBCT images is still a challenging task considering the comparatively low image quality caused by the limited radiation dose, as well as structural ambiguities from intercuspation and nearby alveolar bones. The goal of this paper is to present and discuss the latest accomplishments in semisupervised tooth segmentation with adaptive 3D shape constraints. Methods: The authors propose a 3D exemplar-based random walk method of tooth segmentation from CBCT images. The proposed method integrates semisupervised label propagation and regularization by 3D exemplar registration. To begin with, the pure random walk method is to get an initial segmentation of the teeth, which tends to be erroneous because of the structural ambiguity of CBCT images. And then, as an iterative refinement, the authors conduct a regularization by using 3D exemplar registration, as well as label propagation by random walks with soft constraints, to improve the tooth segmentation. In the first stage of the iteration, 3D exemplars with well-defined topologies are adapted to fit the tooth contours, which are obtained from the random walks based segmentation. The soft constraints on voxel labeling are defined by shape-based foreground dentine probability acquired by the exemplar registration, as well as the appearance-based probability from a support vector machine (SVM) classifier. In the second stage, the labels of the volume-of-interest (VOI) are updated by the random walks with soft constraints. The two stages are optimized iteratively. Instead of the one-shot label propagation in the VOI, an iterative refinement process can achieve a reliable tooth segmentation by virtue of exemplar-based random walks with adaptive soft constraints. Results: The proposed method was applied for tooth segmentation of twenty clinically captured CBCT images. Three metrics, including the Dice similarity coefficient (DSC), the Jaccard similarity coefficient (JSC), and the mean surface deviation (MSD), were used to quantitatively analyze the segmentation of anterior teeth including incisors and canines, premolars, and molars. The segmentation of the anterior teeth achieved a DSC up to 98%, a JSC of 97%, and an MSD of 0.11 mm compared with manual segmentation. For the premolars, the average values of DSC, JSC, and MSD were 98%, 96%, and 0.12 mm, respectively. The proposed method yielded a DSC of 95%, a JSC of 89%, and an MSD of 0.26 mm for molars. Aside from the interactive definition of label priors by the user, automatic tooth segmentation can be achieved in an average of 1.18 min. Conclusions: The proposed technique enables an efficient and reliable tooth segmentation from CBCT images. This study makes it clinically practical to segment teeth from CBCT images, thus facilitating pre- and interoperative uses of dental morphologies in maxillofacial and orthodontic treatments.

60 APPLIED LIFE SCIENCES↗

Prediction of Individual Social-Demographic Role Based on Travel Behavior Variability Using Long-Term GPS Data

With the development of and advances in smartphones and global positioning system (GPS) devices, travelers’ long-term travel behaviors are not impossible to obtain. This study investigates the pattern of individual travel behavior and its correlation with social-demographic features. For different social-demographic groups (e.g., full-time employees and students), the individual travel behavior may have specific temporal-spatial-mobile constraints. The study first extracts the home-based tours, including Home-to-Home and Home-to-Non-Home, from long-term raw GPS data. The travel behavior pattern is then delineated by home-based tour features, such as departure time, destination location entropy, travel time, and driving time ratio. The travel behavior variability describes the variances of travelers’ activity behavior features for an extended period. After that, the variability pattern of an individual’s travel behavior is used for estimating the individual’s social-demographic information, such as social-demographic role, by a supervised learning approach, support vector machine. In this study, a long-term (18-month) recorded GPS data set from Puget Sound Regional Council is used. The experiment’s result is very promising. The sensitivity analysis shows that as the number of tours thresholds increases, the variability of most travel behavior features converges, while the prediction performance may not change for the fixed test data.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Risk Analysis Virtual ENvironment

RAVEN has 3 major functionalities: 1. Provides a Graphical User Interface for the pre- and post-processing of the RELAP-7 input and output. 2. Provides the capability to model nuclear power plants control logic for the RELAP-7 code and dynamic control of the accident scenario evolution. This capability is based on a software structure that realizes a direct connection between the RELAP-7 solver engine (MOOSE) and a python environment where the variables describing the plant status are accessible in a scripting environment. RAVEN support the generation of the probabilistic scenario control by supplying a wide range of probability and cumulative distribution functions and their inverse functions. 3. Provides a general environment to perform probability risk analysis for RELAP-7, RELAP-5 and any generic MOOSE based applications. The probabilistic analysis is performed by sampling the input space of the coupled code parameters and it is enhanced by using modern artificial intelligence algorithms that accelerate the identification of the areas of major risk (in the input parameter space). This environment also provides a graphical visualization capability to analyze the outcomes. Among other approaches, the classical Monte Carlo and Latin Hypercube sampling algorithms are available. For the acceleration of the convergence of the sampling methodologies, Support Vector Machines, Bayesian regression, and collocation stochastic polynomials chaos are implemented. The same methodologies here described could be used to solve optimization and uncertainties propagation problems using the RAVEN framework.

Rabiti, Cristian↗

A Data-Driven Approach for High-Impedance Fault Localization in Distribution Systems [SWR-24-13]

This software provides a data-driven approach for efficiently identifying high impedance faults (HIFs) in distribution systems. To tackle the nonlinearity of the voltage current trajectory of HIFs, we first formulate linear least squares problems to approximate the trajectory with piecewise functions. Then we collect the function features of all segments as inputs and use the support vector machine approach to efficiently identify HIFs at different locations.

Zhou, Yuqi↗

Modeling precision treatment of breast cancer

Background: First-generation molecular profiles for human breast cancers have enabled the identification of features that can predict therapeutic response; however, little is known about how the various data types can best be combined to yield optimal predictors. Collections of breast cancer cell lines mirror many aspects of breast cancer molecular pathobiology, and measurements of their omic and biological therapeutic responses are well-suited for development of strategies to identify the most predictive molecular feature sets. Results: We used least squares-support vector machines and random forest algorithms to identify molecular features associated with responses of a collection of 70 breast cancer cell lines to 90 experimental or approved therapeutic agents. The datasets analyzed included measurements of copy number aberrations, mutations, gene and isoform expression, promoter methylation and protein expression. Transcriptional subtype contributed strongly to response predictors for 25% of compounds, and adding other molecular data types improved prediction for 65%. No single molecular dataset consistently out-performed the others, suggesting that therapeutic response is mediated at multiple levels in the genome. Response predictors were developed and applied to TCGA data, and were found to be present in subsets of those patient samples. Conclusions: These results suggest that matching patients to treatments based on transcriptional subtype will improve response rates, and inclusion of additional features from other profiling data types may provide additional benefit. Further, we suggest a systems biology strategy for guiding clinical trials so that patient cohorts most likely to respond to new therapies may be more efficiently identified.

59 BASIC BIOLOGICAL SCIENCES↗

Discrimination of Mild Cognitive Impairment and Alzheimer′s Disease Using Transfer Entropy Measures of Scalp EEG

Mild cognitive impairment (MCI) is a neurological condition related to early stages of dementia including Alzheimer′s disease (AD). This study investigates the potential of measures of transfer entropy in scalp EEG for effectively discriminating between normal aging, MCI, and AD participants. Resting EEG records from 48 age‐matched participants (mean age 75.7 years)—15 normal controls, 16 MCI, and 17 early AD—are examined. The mean temporal delays corresponding to peaks in inter‐regional transfer entropy are computed and used as features to discriminate between the three groups of participants. Three‐way classification schemes based on binary support vector machine models demonstrate overall discrimination accuracies of 91.7— 93.8%, depending on the protocol condition. These results demonstrate the potential for EEG transfer entropy measures as biomarkers in identifying early MCI and AD. Moreover, the analyses based on short data segments (two minutes) render the method practical for a primary care setting.

McBride, Joseph↗

Segmentation of Multi-Isotope Imaging Mass Spectrometry Data for Semi-Automatic Detection of Regions of Interest

Multi-isotope imaging mass spectrometry (MIMS) associates secondary ion mass spectrometry (SIMS) with detection of several atomic masses, the use of stable isotopes as labels, and affiliated quantitative image-analysis software. By associating image and measure, MIMS allows one to obtain quantitative information about biological processes in subcellular domains. MIMS can be applied to a wide range of biomedical problems, in particular metabolism and cell fate [1,2,3]. In order to obtain morphologically pertinent data from MIMS images, we have to define regions of interest (ROIs). ROIs are drawn by hand, a tedious and time-consuming process. We have developed and successfully applied a support vector machine (SVM) for segmentation of MIMS images that allows fast, semi-automatic boundary detection of regions of interests. Using the SVM, high-quality ROIs (as compared to an expert’s manual delineation) were obtained for 2 types of images derived from unrelated data sets. This automation simplifies, accelerates and improves the post-processing analysis of MIMS images. This approach has been integrated into ‘‘Open MIMS,’’ an ImageJ-plugin for comprehensive analysis of MIMS images that is available online at http://www.nrims.hms.harvard.edu/NRIMS_ImageJ.php.

59 BASIC BIOLOGICAL SCIENCES↗

LABEL: Fast and Accurate Lineage Assignment with Assessment of H5N1 and H9N2 Influenza A Hemagglutinins

The evolutionary classification of influenza genes into lineages is a first step in understanding their molecular epidemiology and can inform the subsequent implementation of control measures. We introduce a novel approach called Lineage Assignment By Extended Learning (LABEL) to rapidly determine cladistic information for any number of genes without the need for time-consuming sequence alignment, phylogenetic tree construction, or manual annotation. Instead, LABEL relies on hidden Markov model profiles and support vector machine training to hierarchically classify gene sequences by their similarity to pre-defined lineages. We assessed LABEL by analyzing the annotated hemagglutinin genes of highly pathogenic (H5N1) and low pathogenicity (H9N2) avian influenza A viruses. Using the WHO/FAO/OIE H5N1 evolution working group nomenclature, the LABEL pipeline quickly and accurately identified the H5 lineages of uncharacterized sequences. Moreover, we developed an updated clade nomenclature for the H9 hemagglutinin gene and show a similarly fast and reliable phylogenetic assessment with LABEL. While this study was focused on hemagglutinin sequences, LABEL could be applied to the analysis of any gene and shows great potential to guide molecular epidemiology activities, accelerate database annotation, and provide a data sorting tool for other large-scale bioinformatic studies.

59 BASIC BIOLOGICAL SCIENCES↗