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1.  Brain extraction from cerebral MRI volume using a hybrid level set based active contour neighborhood model 
Background
The extraction of brain tissue from cerebral MRI volume is an important pre-procedure for neuroimage analyses. The authors have developed an accurate and robust brain extraction method using a hybrid level set based active contour neighborhood model.
Methods
The method uses a nonlinear speed function in the hybrid level set model to eliminate boundary leakage. When using the new hybrid level set model an active contour neighborhood model is applied iteratively in the neighborhood of brain boundary. A slice by slice contour initial method is proposed to obtain the neighborhood of the brain boundary. The method was applied to the internet brain MRI data provided by the Internet Brain Segmentation Repository (IBSR).
Results
In testing, a mean Dice similarity coefficient of 0.95±0.02 and a mean Hausdorff distance of 12.4±4.5 were obtained when performing our method across the IBSR data set (18 × 1.5 mm scans). The results obtained using our method were very similar to those produced using manual segmentation and achieved the smallest mean Hausdorff distance on the IBSR data.
Conclusions
An automatic method of brain extraction from cerebral MRI volume was achieved and produced competitively accurate results.
doi:10.1186/1475-925X-12-31
PMCID: PMC3639852  PMID: 23587217
Brain extraction; Hybrid level set; Active contour neighborhood; MRI volume
2.  Multi-Scale and Shape Constrained Localized Region-Based Active Contour Segmentation of Uterine Fibroid Ultrasound Images in HIFU Therapy 
PLoS ONE  2014;9(7):e103334.
Purpose
To overcome the severe intensity inhomogeneity and blurry boundaries in HIFU (High Intensity Focused Ultrasound) ultrasound images, an accurate and efficient multi-scale and shape constrained localized region-based active contour model (MSLCV), was developed to accurately and efficiently segment the target region in HIFU ultrasound images of uterine fibroids.
Methods
We incorporated a new shape constraint into the localized region-based active contour, which constrained the active contour to obtain the desired, accurate segmentation, avoiding boundary leakage and excessive contraction. Localized region-based active contour modeling is suitable for ultrasound images, but it still cannot acquire satisfactory segmentation for HIFU ultrasound images of uterine fibroids. We improved the localized region-based active contour model by incorporating a shape constraint into region-based level set framework to increase segmentation accuracy. Some improvement measures were proposed to overcome the sensitivity of initialization, and a multi-scale segmentation method was proposed to improve segmentation efficiency. We also designed an adaptive localizing radius size selection function to acquire better segmentation results.
Results
Experimental results demonstrated that the MSLCV model was significantly more accurate and efficient than conventional methods. The MSLCV model has been quantitatively validated via experiments, obtaining an average of 0.94 for the DSC (Dice similarity coefficient) and 25.16 for the MSSD (mean sum of square distance). Moreover, by using the multi-scale segmentation method, the MSLCV model’s average segmentation time was decreased to approximately 1/8 that of the localized region-based active contour model (the LCV model).
Conclusions
An accurate and efficient multi-scale and shape constrained localized region-based active contour model was designed for the semi-automatic segmentation of uterine fibroid ultrasound (UFUS) images in HIFU therapy. Compared with other methods, it provided more accurate and more efficient segmentation results that are very close to those obtained from manual segmentation by a specialist.
doi:10.1371/journal.pone.0103334
PMCID: PMC4111577  PMID: 25061939
3.  An improved level set method for vertebra CT image segmentation 
Background
Clinical diagnosis and therapy for the lumbar disc herniation requires accurate vertebra segmentation. The complex anatomical structure and the degenerative deformations of the vertebrae makes its segmentation challenging.
Methods
An improved level set method, namely edge- and region-based level set method (ERBLS), is proposed for vertebra CT images segmentation. By considering the gradient information and local region characteristics of images, the proposed model can efficiently segment images with intensity inhomogeneity and blurry or discontinuous boundaries. To reduce the dependency on manual initialization in many active contour models and for an automatic segmentation, a simple initialization method for the level set function is built, which utilizes the Otsu threshold. In addition, the need of the costly re-initialization procedure is completely eliminated.
Results
Experimental results on both synthetic and real images demonstrated that the proposed ERBLS model is very robust and efficient. Compared with the well-known local binary fitting (LBF) model, our method is much more computationally efficient and much less sensitive to the initial contour. The proposed method has also applied to 56 patient data sets and produced very promising results.
Conclusions
An improved level set method suitable for vertebra CT images segmentation is proposed. It has the flexibility of segmenting the vertebra CT images with blurry or discontinuous edges, internal inhomogeneity and no need of re-initialization.
doi:10.1186/1475-925X-12-48
PMCID: PMC3701568  PMID: 23714300
Level set method; Image segmentation; Vertebra CT images
4.  Parametric Surface Modeling and Registration for Comparison of Manual and Automated Segmentation of the Hippocampus 
Hippocampus  2009;19(6):588-595.
Accurate and efficient segmentation of the hippocampus from brain images is a challenging issue. Although experienced anatomic tracers can be reliable, manual segmentation is a time consuming process and may not be feasible for large-scale neuroimaging studies. In this paper, we compare an automated method, FreeSurfer (V4), with a published manual protocol on the determination of hippocampal boundaries from MRI scans, using data from an existing MCI/AD cohort. To perform the comparison, we develop an enhanced spherical harmonic processing framework to model and register these hippocampal traces. The framework treats the two hippocampi as a single geometric configuration and extracts the positional, orientation and shape variables in a multi-object setting. We apply this framework to register manual tracing and FreeSurfer results together and the two methods show stronger agreement on position and orientation than shape measures. Work is in progress to examine a refined FreeSurfer segmentation strategy and an improved agreement on shape features is expected.
doi:10.1002/hipo.20613
PMCID: PMC2849649  PMID: 19405146
Shape analysis; segmentation; registration; hippocampus
5.  A Hybrid Geometric–Statistical Deformable Model for Automated 3-D Segmentation in Brain MRI 
We present a novel 3-D deformable model-based approach for accurate, robust, and automated tissue segmentation of brain MRI data of single as well as multiple magnetic resonance sequences. The main contribution of this study is that we employ an edge-based geodesic active contour for the segmentation task by integrating both image edge geometry and voxel statistical homogeneity into a novel hybrid geometric–statistical feature to regularize contour convergence and extract complex anatomical structures. We validate the accuracy of the segmentation results on simulated brain MRI scans of both single T1-weighted and multiple T1/T2/PD-weighted sequences. We also demonstrate the robustness of the proposed method when applied to clinical brain MRI scans. When compared to a current state-of-the-art region-based level-set segmentation formulation, our white matter and gray matter segmentation resulted in significantly higher accuracy levels with a mean improvement in Dice similarity indexes of 8.55% (p < 0.0001) and 10.18% (p < 0.0001), respectively.
doi:10.1109/TBME.2009.2017509
PMCID: PMC3068615  PMID: 19336280
3-D image segmentation; brain segmentation; deformable models; geodesic active contour
6.  Quantitative Evaluation of Automated Skull-Stripping Methods Applied to Contemporary and Legacy Images: Effects of Diagnosis, Bias Correction, and Slice Location 
Human brain mapping  2006;27(2):99-113.
Performance of automated methods to isolate brain from nonbrain tissues in magnetic resonance (MR) structural images may be influenced by MR signal inhomogeneities, type of MR image set, regional anatomy, and age and diagnosis of subjects studied. The present study compared the performance of four methods: Brain Extraction Tool (BET; Smith [2002]: Hum Brain Mapp 17:143–155); 3dIntracranial (Ward [1999] Milwaukee: Biophysics Research Institute, Medical College of Wisconsin; in AFNI); a Hybrid Watershed algorithm (HWA, Segonne et al. [2004] Neuroimage 22:1060–1075; in FreeSurfer); and Brain Surface Extractor (BSE, Sandor and Leahy [1997] IEEE Trans Med Imag 16:41–54; Shattuck et al. [2001] Neuroimage 13:856 – 876) to manually stripped images. The methods were applied to uncorrected and bias-corrected datasets; Legacy and Contemporary T1-weighted image sets; and four diagnostic groups (depressed, Alzheimer’s, young and elderly control). To provide a criterion for outcome assessment, two experts manually stripped six sagittal sections for each dataset in locations where brain and nonbrain tissue are difficult to distinguish. Methods were compared on Jaccard similarity coefficients, Hausdorff distances, and an Expectation-Maximization algorithm. Methods tended to perform better on contemporary datasets; bias correction did not significantly improve method performance. Mesial sections were most difficult for all methods. Although AD image sets were most difficult to strip, HWA and BSE were more robust across diagnostic groups compared with 3dIntracranial and BET. With respect to specificity, BSE tended to perform best across all groups, whereas HWA was more sensitive than other methods. The results of this study may direct users towards a method appropriate to their T1-weighted datasets and improve the efficiency of processing for large, multisite neuroimaging studies.
doi:10.1002/hbm.20161
PMCID: PMC2408865  PMID: 15986433
brain; MRI; Alzheimer’s disease; aging; image processing; statistics
7.  Optimized Brain Extraction for Pathological Brains (optiBET) 
PLoS ONE  2014;9(12):e115551.
The study of structural and functional magnetic resonance imaging data has greatly benefitted from the development of sophisticated and efficient algorithms aimed at automating and optimizing the analysis of brain data. We address, in the context of the segmentation of brain from non-brain tissue (i.e., brain extraction, also known as skull-stripping), the tension between the increased theoretical and clinical interest in patient data, and the difficulty of conventional algorithms to function optimally in the presence of gross brain pathology. Indeed, because of the reliance of many algorithms on priors derived from healthy volunteers, images with gross pathology can severely affect their ability to correctly trace the boundaries between brain and non-brain tissue, potentially biasing subsequent analysis. We describe and make available an optimized brain extraction script for the pathological brain (optiBET) robust to the presence of pathology. Rather than attempting to trace the boundary between tissues, optiBET performs brain extraction by (i) calculating an initial approximate brain extraction; (ii) employing linear and non-linear registration to project the approximate extraction into the MNI template space; (iii) back-projecting a standard brain-only mask from template space to the subject’s original space; and (iv) employing the back-projected brain-only mask to mask-out non-brain tissue. The script results in up to 94% improvement of the quality of extractions over those obtained with conventional software across a large set of severely pathological brains. Since optiBET makes use of freely available algorithms included in FSL, it should be readily employable by anyone having access to such tools.
doi:10.1371/journal.pone.0115551
PMCID: PMC4267825  PMID: 25514672
8.  Region-based progressive localization of cell nuclei in microscopic images with data adaptive modeling 
BMC Bioinformatics  2013;14:173.
Background
Segmenting cell nuclei in microscopic images has become one of the most important routines in modern biological applications. With the vast amount of data, automatic localization, i.e. detection and segmentation, of cell nuclei is highly desirable compared to time-consuming manual processes. However, automated segmentation is challenging due to large intensity inhomogeneities in the cell nuclei and the background.
Results
We present a new method for automated progressive localization of cell nuclei using data-adaptive models that can better handle the inhomogeneity problem. We perform localization in a three-stage approach: first identify all interest regions with contrast-enhanced salient region detection, then process the clusters to identify true cell nuclei with probability estimation via feature-distance profiles of reference regions, and finally refine the contours of detected regions with regional contrast-based graphical model. The proposed region-based progressive localization (RPL) method is evaluated on three different datasets, with the first two containing grayscale images, and the third one comprising of color images with cytoplasm in addition to cell nuclei. We demonstrate performance improvement over the state-of-the-art. For example, compared to the second best approach, on the first dataset, our method achieves 2.8 and 3.7 reduction in Hausdorff distance and false negatives; on the second dataset that has larger intensity inhomogeneity, our method achieves 5% increase in Dice coefficient and Rand index; on the third dataset, our method achieves 4% increase in object-level accuracy.
Conclusions
To tackle the intensity inhomogeneities in cell nuclei and background, a region-based progressive localization method is proposed for cell nuclei localization in fluorescence microscopy images. The RPL method is demonstrated highly effective on three different public datasets, with on average 3.5% and 7% improvement of region- and contour-based segmentation performance over the state-of-the-art.
doi:10.1186/1471-2105-14-173
PMCID: PMC3706337  PMID: 23725412
9.  Intensity Standardization Simplifies Brain MR Image Segmentation 
Typically, brain MR images present significant intensity variation across patients and scanners. Consequently, training a classifier on a set of images and using it subsequently for brain segmentation may yield poor results. Adaptive iterative methods usually need to be employed to account for the variations of the particular scan. These methods are complicated, difficult to implement and often involve significant computational costs. In this paper, a simple, non-iterative method is proposed for brain MR image segmentation. Two preprocessing techniques, namely intensity inhomogeneity correction, and more importantly MR image intensity standardization, used prior to segmentation, play a vital role in making the MR image intensities have a tissue-specific numeric meaning, which leads us to a very simple brain tissue segmentation strategy.
Vectorial scale-based fuzzy connectedness and certain morphological operations are utilized first to generate the brain intracranial mask. The fuzzy membership value of each voxel within the intracranial mask for each brain tissue is then estimated. Finally, a maximum likelihood criterion with spatial constraints taken into account is utilized in classifying all voxels in the intracranial mask into different brain tissue groups. A set of inhomogeneity corrected and intensity standardized images is utilized as a training data set. We introduce two methods to estimate fuzzy membership values. In the first method, called SMG (for simple membership based on a gaussian model), the fuzzy membership value is estimated by fitting a multivariate Gaussian model to the intensity distribution of each brain tissue whose mean intensity vector and covariance matrix are estimated and fixed from the training data sets. The second method, called SMH (for simple membership based on a histogram), estimates fuzzy membership value directly via the intensity distribution of each brain tissue obtained from the training data sets. We present several studies to evaluate the performance of these two methods based on 10 clinical MR images of normal subjects and 10 clinical MR images of Multiple Sclerosis (MS) patients. A quantitative comparison indicates that both methods have overall better accuracy than the k-nearest neighbors (kNN) method, and have much better efficiency than the Finite Mixture (FM) model based Expectation-Maximization (EM) method. Accuracy is similar for our methods and EM method for the normal subject data sets, but much better for our methods for the patient data sets.
doi:10.1016/j.cviu.2009.06.003
PMCID: PMC2777695  PMID: 20161360
Inhomogeneity correction; standardization; fuzzy connectedness; brain image segmentation; MRI
10.  A Semi-automatic Image Segmentation Method for Extraction of Brain Volume from In Vivo Mouse Head Magnetic Resonance Imaging using Constraint Level Sets 
Journal of neuroscience methods  2009;179(2):338-344.
In vivo magnetic resonance imaging (MRI) of mouse brain has been widely used to non-invasively monitor disease progression and/or therapeutic effects in murine models of human neurodegenerative disease. Segmentation of MRI to differentiate brain from non-brain tissue (usually referred to as brain extraction) is required for many MRI data processing and analysis methods, including coregistration, statistical parametric analysis, mapping to brain atlas and histology. This paper presents a semi-automatic brain extraction technique based on a level set method with the incorporation of user-defined constraints. The constraints are derived from the prior knowledge of brain anatomy by defining brain boundary on orthogonal planes of the MRI. Constraints are incorporated in the level set method by spatially varying the weighting factors of the internal and external forces and modifying the image gradient (edge) map. Both two-dimensional multi-slice and three-dimensional versions of the brain extraction technique were developed and applied to MRI data with minimal brain/non-brain contrast T1-weighted (T1-wt) FLASH and maximized contrast T2-weighted (T2-wt) RARE. Results were evaluated by calculating the overlap measure (OM) between the automatically segmented and manually traced brain volumes. Results demonstrate that this technique accurately extracts the brain volume (mean OM = 94 %) and consistently outperformed the region growing method applied to the T2-wt RARE MRI (mean OM = 81 %). This method not only successfully extracts the mouse brain in low and high contrast MRI, but can also be used to segment other organs and tissues.
doi:10.1016/j.jneumeth.2009.02.007
PMCID: PMC2718579  PMID: 19428546
brain extraction; image segmentation; level set; mouse brain; MRI
11.  Automatic Segmentation of Neonatal Images Using Convex Optimization and Coupled Level Sets 
NeuroImage  2011;58(3):805-817.
Accurate segmentation of neonatal brain MR images remains challenging mainly due to their poor spatial resolution, inverted contrast between white matter and gray matter, and high intensity inhomogeneity. Most existing methods for neonatal brain segmentation are atlas-based and voxel-wise. Although active contour/surface models with geometric information constraint have been successfully applied to adult brain segmentation, they are not fully explored in the neonatal image segmentation. In this paper, we propose a novel neonatal image segmentation method by combining local intensity information, atlas spatial prior, and cortical thickness constraint in a single level-set framework. Besides, we also provide a robust and reliable tissue surface initialization for the proposed method by using a convex optimization technique. Thus, tissue segmentation, as well as inner and outer cortical surface reconstruction, can be obtained simultaneously. The proposed method has been tested on a large neonatal dataset, and the validation on 10 neonatal brain images (with manual segmentations) shows very promising results.
doi:10.1016/j.neuroimage.2011.06.064
PMCID: PMC3166374  PMID: 21763443
Neonatal tissue segmentation; atlas-based segmentation; convex optimization; coupled level sets
12.  An Automated Pipeline for Dendrite Spine Detection and Tracking of 3D Optical Microscopy Neuron Images of In Vivo Mouse Models 
Neuroinformatics  2009;7(2):113-130.
The variations in dendritic branch morphology and spine density provide insightful information about the brain function and possible treatment to neurodegenerative disease, for example investigating structural plasticity during the course of Alzheimer's disease. Most automated image processing methods aiming at analyzing these problems are developed for in vitro data. However, in vivo neuron images provide real time information and direct observation of the dynamics of a disease process in a live animal model. This paper presents an automated approach for detecting spines and tracking spine evolution over time with in vivo image data in an animal model of Alzheimer's disease. We propose an automated pipeline starting with curvilinear structure detection to determine the medial axis of the dendritic backbone and spines connected to the backbone. We, then, propose the adaptive local binary fitting (aLBF) energy level set model to accurately locate the boundary of dendritic structures using the central line of curvilinear structure as initialization. To track the growth or loss of spines, we present a maximum likelihood based technique to find the graph homomorphism between two image graph structures at different time points. We employ dynamic programming to search for the optimum solution. The pipeline enables us to extract dynamically changing information from real time in vivo data. We validate our proposed approach by comparing with manual results generated by neurologists. In addition, we discuss the performance of 3D based segmentation and conclude that our method is more accurate in identifying weak spines. Experiments show that our approach can quickly and accurately detect and quantify spines of in vivo neuron images and is able to identify spine elimination and formation.
doi:10.1007/s12021-009-9047-0
PMCID: PMC2872186  PMID: 19434521
Dendrite spine detection; Quantification; Tracking; Level set; In vivo image
13.  Level set segmentation of bovine corpora lutea in ex situ ovarian ultrasound images 
Background
The objective of this study was to investigate the viability of level set image segmentation methods for the detection of corpora lutea (corpus luteum, CL) boundaries in ultrasonographic ovarian images. It was hypothesized that bovine CL boundaries could be located within 1–2 mm by a level set image segmentation methodology.
Methods
Level set methods embed a 2D contour in a 3D surface and evolve that surface over time according to an image-dependent speed function. A speed function suitable for segmentation of CL's in ovarian ultrasound images was developed. An initial contour was manually placed and contour evolution was allowed to proceed until the rate of change of the area was sufficiently small. The method was tested on ovarian ultrasonographic images (n = 8) obtained ex situ. A expert in ovarian ultrasound interpretation delineated CL boundaries manually to serve as a "ground truth". Accuracy of the level set segmentation algorithm was determined by comparing semi-automatically determined contours with ground truth contours using the mean absolute difference (MAD), root mean squared difference (RMSD), Hausdorff distance (HD), sensitivity, and specificity metrics.
Results and discussion
The mean MAD was 0.87 mm (sigma = 0.36 mm), RMSD was 1.1 mm (sigma = 0.47 mm), and HD was 3.4 mm (sigma = 2.0 mm) indicating that, on average, boundaries were accurate within 1–2 mm, however, deviations in excess of 3 mm from the ground truth were observed indicating under- or over-expansion of the contour. Mean sensitivity and specificity were 0.814 (sigma = 0.171) and 0.990 (sigma = 0.00786), respectively, indicating that CLs were consistently undersegmented but rarely did the contour interior include pixels that were judged by the human expert not to be part of the CL. It was observed that in localities where gradient magnitudes within the CL were strong due to high contrast speckle, contour expansion stopped too early.
Conclusion
The hypothesis that level set segmentation can be accurate to within 1–2 mm on average was supported, although there can be some greater deviation. The method was robust to boundary leakage as evidenced by the high specificity. It was concluded that the technique is promising and that a suitable data set of human ovarian images should be obtained to conduct further studies.
doi:10.1186/1477-7827-6-33
PMCID: PMC2519064  PMID: 18680589
14.  Automated Detection of Breast Mass Spiculation Levels and Evaluation of Scheme Performance 
Academic radiology  2008;15(12):1534-1544.
Rationale and Objectives
Although spiculation level of breast mass boundary is a primary sign of malignancy for the mass detected on mammograms, developing an automated computer scheme to detect mass spiculation level and quantitatively evaluating the performance of the scheme is a difficult task. The objective of this study is to (1) develop and test a new scheme to improve mass segmentation and detect mass boundary spiculation level, and (2) assess the scheme performance using a relatively large image dataset.
Materials and Methods
This fully-automated scheme includes three image processing steps. The first step applies the maximum entropy principle in the selected region of interest (ROI) after correcting the background-trend to enhance the initial outlines of the masses. The second step uses an active contour model to refine the initial outlines. The third step detects and identifies spiculated lines connected to the mass boundary using a special line detector. A quantitative spiculation index is computed to assess the degree of spiculation levels. To develop and evaluate this automated scheme, we selected 211 ROIs depicting masses that were extracted from a publicly available image database. Among these ROIs, 106 depict “circumscribed” mass regions and 105 involve “spiculated” mass regions. The scheme performance was evaluated using the receiver operating characteristic (ROC) analysis method.
Results
The computed area under ROC curve when applying the scheme to the dataset is 0.701 ± 0.027. By setting up a threshold at spiculation index = 5.0, the scheme achieves the overall classification accuracy of 66.4% with 54.3% sensitivity and 78.3% specificity, respectively.
Conclusions
We developed a new computer scheme with a number of unique characteristics to detect spiculated mass regions and applied a simple spiculation index to quantify mass spiculation levels. Although this quantitative index can be used to classify between the spiculated and circumscribed masses, the results also suggest that automated detection of mass spiculation levels remains a technical challenge.
doi:10.1016/j.acra.2008.07.015
PMCID: PMC2857703  PMID: 19000870
Computer-aided diagnosis; mammography; mass segmentation; mass spiculations
15.  Computer-aided diagnosis of pulmonary nodules on CT scans: Segmentation and classification using 3D active contours 
Medical physics  2006;33(7):2323-2337.
We are developing a computer-aided diagnosis (CAD) system to classify malignant and benign lung nodules found on CT scans. A fully automated system was designed to segment the nodule from its surrounding structured background in a local volume of interest (VOI) and to extract image features for classification. Image segmentation was performed with a three-dimensional (3D) active contour (AC) method. A data set of 96 lung nodules (44 malignant, 52 benign) from 58 patients was used in this study. The 3D AC model is based on two-dimensional AC with the addition of three new energy components to take advantage of 3D information: (1) 3D gradient, which guides the active contour to seek the object surface, (2) 3D curvature, which imposes a smoothness constraint in the z direction, and (3) mask energy, which penalizes contours that grow beyond the pleura or thoracic wall. The search for the best energy weights in the 3D AC model was guided by a simplex optimization method. Morphological and gray-level features were extracted from the segmented nodule. The rubber band straightening transform (RBST) was applied to the shell of voxels surrounding the nodule. Texture features based on run-length statistics were extracted from the RBST image. A linear discriminant analysis classifier with stepwise feature selection was designed using a second simplex optimization to select the most effective features. Leave-one-case-out resampling was used to train and test the CAD system. The system achieved a test area under the receiver operating characteristic curve (Az) of 0.83±0.04. Our preliminary results indicate that use of the 3D AC model and the 3D texture features surrounding the nodule is a promising approach to the segmentation and classification of lung nodules with CAD. The segmentation performance of the 3D AC model trained with our data set was evaluated with 23 nodules available in the Lung Image Database Consortium (LIDC). The lung nodule volumes segmented by the 3D AC model for best classification were generally larger than those outlined by the LIDC radiologists using visual judgment of nodule boundaries.
doi:10.1118/1.2207129
PMCID: PMC2728558  PMID: 16898434
computer-aided diagnosis; active contour model; object segmentation; classification; texture analysis; computed tomography (CT); malignancy; pulmonary nodule
16.  Segmentation of 3D Radio Frequency Echocardiography Using a Spatio-temporal Predictor 
Medical Image Analysis  2011;16(2):351-360.
This paper presents an algorithm for segmenting left ventricular endocardial boundaries from RF ultrasound. Our method incorporates a computationally efficient linear predictor that exploits short-term spatio-temporal coherence in the RF data. Segmentation is achieved jointly using an independent identically distributed (i.i.d.) spatial model for RF intensity and a multiframe conditional model that relates neighboring frames in the image sequence. Segmentation using the RF data overcomes challenges due to image inhomogeneities often amplified in B-mode segmentation and provides geometric constraints for RF phase-based speckle tracking. The incorporation of multiple frames in the conditional model significantly increases the robustness and accuracy of the algorithm. Results are generated using between 2 and 5 frames of RF data for each segmentation and are validated by comparison with manual tracings and automated B-mode boundary detection using standard (Chan and Vese-based) level sets on echocardiographic images from 27 3D sequences acquired from 6 canine studies.
doi:10.1016/j.media.2011.09.002
PMCID: PMC3267850  PMID: 22078842
Ultrasound; Cardiac imaging; Segmentation; Radiofrequency signal
17.  Automated ventricular mapping with multi-atlas fluid image alignment reveals genetic effects in Alzheimer’s disease 
NeuroImage  2007;40(2):615-630.
We developed and validated a new method to create automated 3D parametric surface models of the lateral ventricles in brain MRI scans, providing an efficient approach to monitor degenerative disease in clinical studies and drug trials. First, we used a set of parameterized surfaces to represent the ventricles in four subjects’ manually labeled brain MRI scans (atlases). We fluidly registered each atlas and mesh model to MRIs from 17 Alzheimer’s disease (AD) patients and 13 age-and gender-matched healthy elderly control subjects, and 18 asymptomatic ApoE4-carriers and 18 age- and gender-matched non-carriers. We examined genotyped healthy subjects with the goal of detecting subtle effects of a gene that confers heightened risk for Alzheimer’s disease. We averaged the meshes extracted for each 3D MR data set, and combined the automated segmentations with a radial mapping approach to localize ventricular shape differences in patients. Validation experiments comparing automated and expert manual segmentations showed that (1) the Hausdorff labeling error rapidly decreased, and (2) the power to detect disease- and gene-related alterations improved, as the number of atlases, N, was increased from 1 to 9. In surface-based statistical maps, we detected more widespread and intense anatomical deficits as we increased the number of atlases. We formulated a statistical stopping criterion to determine the optimal number of atlases to use. Healthy ApoE4-carriers and those with AD showed local ventricular abnormalities. This high-throughput method for morphometric studies further motivates the combination of genetic and neuroimaging strategies in predicting AD progression and treatment response.
doi:10.1016/j.neuroimage.2007.11.047
PMCID: PMC2720413  PMID: 18222096
18.  Ranked retrieval of segmented nuclei for objective assessment of cancer gene repositioning 
BMC Bioinformatics  2012;13:232.
Background
Correct segmentation is critical to many applications within automated microscopy image analysis. Despite the availability of advanced segmentation algorithms, variations in cell morphology, sample preparation, and acquisition settings often lead to segmentation errors. This manuscript introduces a ranked-retrieval approach using logistic regression to automate selection of accurately segmented nuclei from a set of candidate segmentations. The methodology is validated on an application of spatial gene repositioning in breast cancer cell nuclei. Gene repositioning is analyzed in patient tissue sections by labeling sequences with fluorescence in situ hybridization (FISH), followed by measurement of the relative position of each gene from the nuclear center to the nuclear periphery. This technique requires hundreds of well-segmented nuclei per sample to achieve statistical significance. Although the tissue samples in this study contain a surplus of available nuclei, automatic identification of the well-segmented subset remains a challenging task.
Results
Logistic regression was applied to features extracted from candidate segmented nuclei, including nuclear shape, texture, context, and gene copy number, in order to rank objects according to the likelihood of being an accurately segmented nucleus. The method was demonstrated on a tissue microarray dataset of 43 breast cancer patients, comprising approximately 40,000 imaged nuclei in which the HES5 and FRA2 genes were labeled with FISH probes. Three trained reviewers independently classified nuclei into three classes of segmentation accuracy. In man vs. machine studies, the automated method outperformed the inter-observer agreement between reviewers, as measured by area under the receiver operating characteristic (ROC) curve. Robustness of gene position measurements to boundary inaccuracies was demonstrated by comparing 1086 manually and automatically segmented nuclei. Pearson correlation coefficients between the gene position measurements were above 0.9 (p < 0.05). A preliminary experiment was conducted to validate the ranked retrieval in a test to detect cancer. Independent manual measurement of gene positions agreed with automatic results in 21 out of 26 statistical comparisons against a pooled normal (benign) gene position distribution.
Conclusions
Accurate segmentation is necessary to automate quantitative image analysis for applications such as gene repositioning. However, due to heterogeneity within images and across different applications, no segmentation algorithm provides a satisfactory solution. Automated assessment of segmentations by ranked retrieval is capable of reducing or even eliminating the need to select segmented objects by hand and represents a significant improvement over binary classification. The method can be extended to other high-throughput applications requiring accurate detection of cells or nuclei across a range of biomedical applications.
doi:10.1186/1471-2105-13-232
PMCID: PMC3484015  PMID: 22971117
19.  Pediatric Brain Extraction Using Learning-based Meta-algorithm 
NeuroImage  2012;62(3):1975-1986.
Magnetic resonance imaging of pediatric brain provides valuable information for early brain development studies. Automated brain extraction is challenging due to the small brain size and dynamic change of tissue contrast in the developing brains. In this paper, we propose a novel Learning Algorithm for Brain Extraction and Labeling (LABEL) specially for the pediatric MR brain images. The idea is to perform multiple complementary brain extractions on a given testing image by using a meta-algorithm, including BET and BSE, where the parameters of each run of the meta-algorithm are effectively learned from the training data. Also, the representative subjects are selected as exemplars and used to guide brain extraction of new subjects in different age groups. We further develop a level-set based fusion method to combine multiple brain extractions together with a closed smooth surface for obtaining the final extraction. The proposed method has been extensively evaluated in subjects of three representative age groups, such as neonate (less than 2 months), infant (1–2 years), and child (5–18 years). Experimental results show that, with 45 subjects for training (15 neonates, 15 infant, and 15 children), the proposed method can produce more accurate brain extraction results on 246 testing subjects (75 neonates, 126 infants, and 45 children), i.e., at average Jaccard Index of 0.953, compared to those by BET (0.918), BSE (0.902), ROBEX (0.901), GCUT (0.856), and other fusion methods such as Majority Voting (0.919) and STAPLE (0.941). Along with the largely-improved computational efficiency, the proposed method demonstrates its ability of automated brain extraction for pediatric MR images in a large age range.
doi:10.1016/j.neuroimage.2012.05.042
PMCID: PMC3408835  PMID: 22634859
Meta-algorithm; Skull stripping; Brain extraction; Label fusion; Level-set; Affinity propagation; Infant brain analysis
20.  Detection of Pulmonary Nodules in CT Images Based on Fuzzy Integrated Active Contour Model and Hybrid Parametric Mixture Model 
The segmentation and detection of various types of nodules in a Computer-aided detection (CAD) system present various challenges, especially when (1) the nodule is connected to a vessel and they have very similar intensities; (2) the nodule with ground-glass opacity (GGO) characteristic possesses typical weak edges and intensity inhomogeneity, and hence it is difficult to define the boundaries. Traditional segmentation methods may cause problems of boundary leakage and “weak” local minima. This paper deals with the above mentioned problems. An improved detection method which combines a fuzzy integrated active contour model (FIACM)-based segmentation method, a segmentation refinement method based on Parametric Mixture Model (PMM) of juxta-vascular nodules, and a knowledge-based C-SVM (Cost-sensitive Support Vector Machines) classifier, is proposed for detecting various types of pulmonary nodules in computerized tomography (CT) images. Our approach has several novel aspects: (1) In the proposed FIACM model, edge and local region information is incorporated. The fuzzy energy is used as the motivation power for the evolution of the active contour. (2) A hybrid PMM Model of juxta-vascular nodules combining appearance and geometric information is constructed for segmentation refinement of juxta-vascular nodules. Experimental results of detection for pulmonary nodules show desirable performances of the proposed method.
doi:10.1155/2013/515386
PMCID: PMC3652289  PMID: 23690876
21.  Brain MAPS: an automated, accurate and robust brain extraction technique using a template library 
NeuroImage  2010;55(3):1091-1108.
Whole brain extraction is an important pre-processing step in neuro-image analysis. Manual or semi-automated brain delineations are labour-intensive and thus not desirable in large studies, meaning that automated techniques are preferable. The accuracy and robustness of automated methods are crucial because human expertise may be required to correct any sub-optimal results, which can be very time consuming. We compared the accuracy of four automated brain extraction methods: Brain Extraction Tool (BET), Brain Surface Extractor (BSE), Hybrid Watershed Algorithm (HWA) and a Multi-Atlas Propagation and Segmentation (MAPS) technique we have previously developed for hippocampal segmentation. The four methods were applied to extract whole brains from 682 1.5T and 157 3T T1-weighted MR baseline images from the Alzheimer’s Disease Neuroimaging Initiative database. Semi-automated brain segmentations with manual editing and checking were used as the gold-standard to compare with the results. The median Jaccard index of MAPS was higher than HWA, BET and BSE in 1.5T and 3T scans (p < 0.05, all tests), and the 1st-99th centile range of the Jaccard index of MAPS was smaller than HWA, BET and BSE in 1.5T and 3T scans (p < 0.05, all tests). HWA and MAPS were found to be best at including all brain tissues (median false negative rate ≤ 0.010% for 1.5T scans and ≤ 0.019% for 3T scans, both methods). The median Jaccard index of MAPS were similar in both 1.5T and 3T scans, whereas those of BET, BSE and HWA were higher in 1.5T scans than 3T scans (p < 0.05, all tests). We found that the diagnostic group had a small effect on the median Jaccard index of all four methods. In conclusion, MAPS had relatively high accuracy and low variability compared to HWA, BET and BSE in MR scans with and without atrophy.
doi:10.1016/j.neuroimage.2010.12.067
PMCID: PMC3554789  PMID: 21195780
Automated brain extraction; skull-stripping; segmentation; MAPS; BET; BSE; HWA
22.  Magnetic resonance image tissue classification using an automatic method 
Diagnostic Pathology  2014;9(1):207.
Background
Brain segmentation in magnetic resonance images (MRI) is an important stage in clinical studies for different issues such as diagnosis, analysis, 3-D visualizations for treatment and surgical planning. MR Image segmentation remains a challenging problem in spite of different existing artifacts such as noise, bias field, partial volume effects and complexity of the images. Some of the automatic brain segmentation techniques are complex and some of them are not sufficiently accurate for certain applications. The goal of this paper is proposing an algorithm that is more accurate and less complex).
Methods
In this paper we present a simple and more accurate automated technique for brain segmentation into White Matter, Gray Matter and Cerebrospinal fluid (CSF) in three-dimensional MR images. The algorithm’s three steps are histogram based segmentation, feature extraction and final classification using SVM. The integrated algorithm has more accurate results than what can be obtained with its individual components. To produce much more efficient segmentation method our framework captures different types of features in each step that are of special importance for MRI, i.e., distributions of tissue intensities, textural features, and relationship with neighboring voxels or spatial features.
Results
Our method has been validated on real images and simulated data, with desirable performance in the presence of noise and intensity inhomogeneities.
Conclusions
The experimental results demonstrate that our proposed method is a simple and accurate technique to define brain tissues with high reproducibility in comparison with other techniques.
Virtual Slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_207
doi:10.1186/s13000-014-0207-7
PMCID: PMC4300026  PMID: 25540017
Statistical segmentation; Magnetic resonance imaging; Image segmentation; Histogram-based segmentation method; SVMs; Brain tissue classification
23.  A Hybrid Hierarchical Approach for Brain Tissue Segmentation by Combining Brain Atlas and Least Square Support Vector Machine 
In this paper, we present a new semi-automatic brain tissue segmentation method based on a hybrid hierarchical approach that combines a brain atlas as a priori information and a least-square support vector machine (LS-SVM). The method consists of three steps. In the first two steps, the skull is removed and the cerebrospinal fluid (CSF) is extracted. These two steps are performed using the toolbox FMRIB's automated segmentation tool integrated in the FSL software (FSL-FAST) developed in Oxford Centre for functional MRI of the brain (FMRIB). Then, in the third step, the LS-SVM is used to segment grey matter (GM) and white matter (WM). The training samples for LS-SVM are selected from the registered brain atlas. The voxel intensities and spatial positions are selected as the two feature groups for training and test. SVM as a powerful discriminator is able to handle nonlinear classification problems; however, it cannot provide posterior probability. Thus, we use a sigmoid function to map the SVM output into probabilities. The proposed method is used to segment CSF, GM and WM from the simulated magnetic resonance imaging (MRI) using Brainweb MRI simulator and real data provided by Internet Brain Segmentation Repository. The semi-automatically segmented brain tissues were evaluated by comparing to the corresponding ground truth. The Dice and Jaccard similarity coefficients, sensitivity and specificity were calculated for the quantitative validation of the results. The quantitative results show that the proposed method segments brain tissues accurately with respect to corresponding ground truth.
PMCID: PMC3967426  PMID: 24696800
Atlas; brain; magnetic resonance imaging; segmentation; support vector machines
24.  Segmentation of Intensity Inhomogeneous Brain MR Images Using Active Contours 
Segmentation of intensity inhomogeneous regions is a well-known problem in image analysis applications. This paper presents a region-based active contour method for image segmentation, which properly works in the context of intensity inhomogeneity problem. The proposed region-based active contour method embeds both region and gradient information unlike traditional methods. It contains mainly two terms, area and length, in which the area term practices a new region-based signed pressure force (SPF) function, which utilizes mean values from a certain neighborhood using the local binary fitted (LBF) energy model. In turn, the length term uses gradient information. The novelty of our method is to locally compute new SPF function, which uses local mean values and is able to detect boundaries of the homogenous regions. Finally, a truncated Gaussian kernel is used to regularize the level set function, which not only regularizes it but also removes the need of computationally expensive reinitialization. The proposed method targets the segmentation problem of intensity inhomogeneous images and reduces the time complexity among locally computed active contour methods. The experimental results show that the proposed method yields better segmentation result as well as less time complexity compared with the state-of-the-art active contour methods.
doi:10.1155/2014/194614
PMCID: PMC4124790  PMID: 25143780
25.  A Comparison of Supervised Machine Learning Algorithms and Feature Vectors for MS Lesion Segmentation Using Multimodal Structural MRI 
PLoS ONE  2014;9(4):e95753.
Machine learning is a popular method for mining and analyzing large collections of medical data. We focus on a particular problem from medical research, supervised multiple sclerosis (MS) lesion segmentation in structural magnetic resonance imaging (MRI). We examine the extent to which the choice of machine learning or classification algorithm and feature extraction function impacts the performance of lesion segmentation methods. As quantitative measures derived from structural MRI are important clinical tools for research into the pathophysiology and natural history of MS, the development of automated lesion segmentation methods is an active research field. Yet, little is known about what drives performance of these methods. We evaluate the performance of automated MS lesion segmentation methods, which consist of a supervised classification algorithm composed with a feature extraction function. These feature extraction functions act on the observed T1-weighted (T1-w), T2-weighted (T2-w) and fluid-attenuated inversion recovery (FLAIR) MRI voxel intensities. Each MRI study has a manual lesion segmentation that we use to train and validate the supervised classification algorithms. Our main finding is that the differences in predictive performance are due more to differences in the feature vectors, rather than the machine learning or classification algorithms. Features that incorporate information from neighboring voxels in the brain were found to increase performance substantially. For lesion segmentation, we conclude that it is better to use simple, interpretable, and fast algorithms, such as logistic regression, linear discriminant analysis, and quadratic discriminant analysis, and to develop the features to improve performance.
doi:10.1371/journal.pone.0095753
PMCID: PMC4004572  PMID: 24781953

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