Prediction-oriented prognostic biomarker discovery with survival machine learning methods.

Identifying novel and reliable prognostic biomarkers for predicting patient survival outcomes is essential for deciding personalized treatment strategies for diseases such as cancer. Numerous feature selection techniques have been proposed to address the high-dimensional problem in constructing prediction models. Not only does feature selection lower the data dimension, but it also improves the prediction accuracy of the resulted models by mitigating overfitting. The performances of these feature selection methods when applied to survival models, on the other hand, deserve further investigation. In this paper, we construct and compare a series of prediction-oriented biomarker selection frameworks by leveraging recent machine learning algorithms, including random survival forests, extreme gradient boosting, light gradient boosting and deep learning-based survival models. Additionally, we adapt the recently proposed prediction-oriented marker selection (PROMISE) to a survival model (PROMISE-Cox) as a benchmark approach. Our simulation studies indicate that boosting-based approaches tend to provide superior accuracy with better true positive rate and false positive rate in more complicated scenarios. For demonstration purpose, we applied the proposed biomarker selection strategies to identify prognostic biomarkers in different modalities of head and neck cancer data.

Predicting 3D dose distribution with scale attention network for prostate cancer radiotherapy.

The growing demand for radiation therapy to treat cancer has been directed to focus on improving treatment planning flow for patients. Accurate dose prediction, therefore, plays a prominent role in this regard. In this study, we propose a framework based on our newly developed scale attention networks (SA-Net) to attain voxel-wise dose prediction. Our network 's dynamic scale attention model incorporates low-level details with high-level semantics from feature maps at different scales. To achieve more accurate results, we used distance data between each local voxel and the organ surfaces instead of binary masks of organs at risk as well as CT image as input of the network. The proposed method is tested on prostate cancer treated with Volumetric Modulated Arc Therapy (VMAT), where the model was training with 120 cases and tested on 20 cases. The average dose difference between the predicted dose and the clinical planned dose was 0.94 Gy, which is equivalent to 2.1% as compared to the prescription dose of 45 Gy. We also compared the performance of SA-Net dose prediction framework with different input format, the signed distance map vs. binary mask and showed the signed distance map was a better format as input to the model training. These findings show that our deep learning-based strategy of dose prediction is effectively feasible for automating the treatment planning in prostate cancer radiography.

Head and neck tumor segmentation in PET/CT: The HECKTOR challenge.

This paper relates the post-analysis of the first edition of the HEad and neCK TumOR (HECKTOR) challenge. This challenge was held as a satellite event of the 23rd International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020, and was the first of its kind focusing on lesion segmentation in combined FDG-PET and CT image modalities. The challenge's task is the automatic segmentation of the Gross Tumor Volume (GTV) of Head and Neck (H&N) oropharyngeal primary tumors in FDG-PET/CT images. To this end, the participants were given a training set of 201 cases from four different centers and their methods were tested on a held-out set of 53 cases from a fifth center. The methods were ranked according to the Dice Score Coefficient (DSC) averaged across all test cases. An additional inter-observer agreement study was organized to assess the difficulty of the task from a human perspective. 64 teams registered to the challenge, among which 10 provided a paper detailing their approach. The best method obtained an average DSC of 0.7591, showing a large improvement over our proposed baseline method and the inter-observer agreement, associated with DSCs of 0.6610 and 0.61, respectively. The automatic methods proved to successfully leverage the wealth of metabolic and structural properties of combined PET and CT modalities, significantly outperforming human inter-observer agreement level, semi-automatic thresholding based on PET images as well as other single modality-based methods. This promising performance is one step forward towards large-scale radiomics studies in H&N cancer, obviating the need for error-prone and time-consuming manual delineation of GTVs.

Improving Dermoscopic Image Segmentation with Enhanced Convolutional-Deconvolutional Networks.

Automatic skin lesion segmentation on dermoscopic images is an essential step in computer-aided diagnosis of melanoma. However, this task is challenging due to significant variations of lesion appearances across different patients. This challenge is further exacerbated when dealing with a large amount of image data. In this paper, we extended our previous work by developing a deeper network architecture with smaller kernels to enhance its discriminant capacity. In addition, we explicitly included color information from multiple color spaces to facilitate network training and thus to further improve the segmentation performance. We participated and extensively evaluated our method on the ISBI 2017 skin lesion segmentation challenge. By training with the 2000 challenge training images, our method achieved an average Jaccard Index (JA) of 0:765 on the 600 challenge testing images, which ranked itself in the first place among 21 final submissions in the challenge.

Three-dimensional cluster formation and structure in heterogeneous dose distribution of intensity modulated radiation therapy.

PURPOSE: To investigate three-dimensional cluster structure and its correlation to clinical endpoint in heterogeneous dose distributions from intensity modulated radiation therapy. METHODS: Twenty-five clinical plans from twenty-one head and neck (HN) patients were used for a phenomenological study of the cluster structure formed from the dose distributions of organs at risks (OARs) close to the planning target volumes (PTVs). Initially, OAR clusters were searched to examine the pattern consistence among ten HN patients and five clinically similar plans from another HN patient. Second, clusters of the esophagus from another ten HN patients were scrutinized to correlate their sizes to radiobiological parameters. Finally, an extensive Monte Carlo (MC) procedure was implemented to gain deeper insights into the behavioral properties of the cluster formation. RESULTS: Clinical studies showed that OAR clusters had drastic differences despite similar PTV coverage among different patients, and the radiobiological parameters failed to positively correlate with the cluster sizes. MC study demonstrated the inverse relationship between the cluster size and the cluster connectivity, and the nonlinear changes in cluster size with dose thresholds. In addition, the clusters were insensitive to the shape of OARs. CONCLUSION: The results demonstrated that the cluster size could serve as an insightful index of normal tissue damage. The clinical outcome of the same dose-volume might be potentially different.

Computed tomography-based treatment planning for high-dose-rate brachytherapy using the tandem and ring applicator: influence of applicator choice on organ dose and inter-fraction adaptive planning.

Three dimensional planning for high-dose-rate (HDR) brachytherapy in cervical cancer has been highly recommended by consensus guidelines such as the American Brachytherapy Society (ABS) and the Groupe Européen de Curiethérapie - European Society for Radiotherapy and Oncology (GEC-ESTRO). In this document, we describe our experience with computed tomography (CT)-based planning using the tandem/ring applicator. We discuss the influence of applicator geometry on doses to organs at risk (OARs), namely the bladder, rectum, and sigmoid. Through example cases with dose prescribed to point A, we demonstrate how adaptive planning can help achieve constraints to the OARs as per guidelines.

Automatic Skin Lesion Segmentation Using Deep Fully Convolutional Networks With Jaccard Distance.

Automatic skin lesion segmentation in dermoscopic images is a challenging task due to the low contrast between lesion and the surrounding skin, the irregular and fuzzy lesion borders, the existence of various artifacts, and various imaging acquisition conditions. In this paper, we present a fully automatic method for skin lesion segmentation by leveraging 19-layer deep convolutional neural networks that is trained end-to-end and does not rely on prior knowledge of the data. We propose a set of strategies to ensure effective and efficient learning with limited training data. Furthermore, we design a novel loss function based on Jaccard distance to eliminate the need of sample re-weighting, a typical procedure when using cross entropy as the loss function for image segmentation due to the strong imbalance between the number of foreground and background pixels. We evaluated the effectiveness, efficiency, as well as the generalization capability of the proposed framework on two publicly available databases. One is from ISBI 2016 skin lesion analysis towards melanoma detection challenge, and the other is the PH2 database. Experimental results showed that the proposed method outperformed other state-of-the-art algorithms on these two databases. Our method is general enough and only needs minimum pre- and post-processing, which allows its adoption in a variety of medical image segmentation tasks.

Robust breathing signal extraction from cone beam CT projections based on adaptive and global optimization techniques.

We present a study of extracting respiratory signals from cone beam computed tomography (CBCT) projections within the framework of the Amsterdam Shroud (AS) technique. Acquired prior to the radiotherapy treatment, CBCT projections were preprocessed for contrast enhancement by converting the original intensity images to attenuation images with which the AS image was created. An adaptive robust z-normalization filtering was applied to further augment the weak oscillating structures locally. From the enhanced AS image, the respiratory signal was extracted using a two-step optimization approach to effectively reveal the large-scale regularity of the breathing signals. CBCT projection images from five patients acquired with the Varian Onboard Imager on the Clinac iX System Linear Accelerator (Varian Medical Systems, Palo Alto, CA) were employed to assess the proposed technique. Stable breathing signals can be reliably extracted using the proposed algorithm. Reference waveforms obtained using an air bellows belt (Philips Medical Systems, Cleveland, OH) were exported and compared to those with the AS based signals. The average errors for the enrolled patients between the estimated breath per minute (bpm) and the reference waveform bpm can be as low as -0.07 with the standard deviation 1.58. The new algorithm outperformed the original AS technique for all patients by 8.5% to 30%. The impact of gantry rotation on the breathing signal was assessed with data acquired with a Quasar phantom (Modus Medical Devices Inc., London, Canada) and found to be minimal on the signal frequency. The new technique developed in this work will provide a practical solution to rendering markerless breathing signal using the CBCT projections for thoracic and abdominal patients.

A Feasibility Study of Tumor Motion Estimate With Regional Deformable Registration Method for 4-Dimensional Radiation Therapy of Lung Cancer.

This study aims to employ 4-dimensional computed tomography to quantify intrafractional tumor motion for patients with lung cancer to improve target localization in radiation therapy. A multistage regional deformable registration was implemented to calculate the excursion of gross tumor volume (GTV) during a breathing cycle. GTV was initially delineated on 0% phase of 4-dimensional computed tomography manually, and a subregion with 20 mm margin supplemented to GTV was generated with Eclipse treatment planning system (Varian Medical Systems, Palo Alto, California). The structures, together with the 4-dimensional computed tomography set, were exported into an in-house software, with which a 3-stage B-spline deformable registration was carried out to map the subregion and warp GTV contour to other breathing phases. The center of mass of the GTV was computed using the contours, and the tumor motion was appraised as the excursion of the center of mass between 0% phase and other phases. Application of the algorithm to the 10 patients showed that clinically satisfactory outcomes were achievable with a spatial accuracy around 2 mm for GTV contour propagation between adjacent phases and 3 mm between opposite phases. The tumor excursion was determined in the vast range of 1 mm through 1.6 cm, depending on the tumor location and tumor size. Compared to the traditional whole image-based registration, the regional method was found computationally a factor of 5 more efficient. The proposed technique has demonstrated its capability in extracting thoracic tumor motion and should find its application in 4-dimensional radiation therapy in the future to maximally utilize the available spatial-temporal information.

Tracking fuzzy borders using geodesic curves with application to liver segmentation on planning CT.

PURPOSE: This work aims to develop a robust and efficient method to track the fuzzy borders between liver and the abutted organs where automatic liver segmentation usually suffers, and to investigate its applications in automatic liver segmentation on noncontrast-enhanced planning computed tomography (CT) images. METHODS: In order to track the fuzzy liver-chestwall and liver-heart borders where oversegmentation is often found, a starting point and an ending point were first identified on the coronal view images; the fuzzy border was then determined as a geodesic curve constructed by minimizing the gradient-weighted path length between these two points near the fuzzy border. The minimization of path length was numerically solved by fast-marching method. The resultant fuzzy borders were incorporated into the authors' automatic segmentation scheme, in which the liver was initially estimated by a patient-specific adaptive thresholding and then refined by a geodesic active contour model. By using planning CT images of 15 liver patients treated with stereotactic body radiation therapy, the liver contours extracted by the proposed computerized scheme were compared with those manually delineated by a radiation oncologist. RESULTS: The proposed automatic liver segmentation method yielded an average Dice similarity coefficient of 0.930 ± 0.015, whereas it was 0.912 ± 0.020 if the fuzzy border tracking was not used. The application of fuzzy border tracking was found to significantly improve the segmentation performance. The mean liver volume obtained by the proposed method was 1727 cm(3), whereas it was 1719 cm(3) for manual-outlined volumes. The computer-generated liver volumes achieved excellent agreement with manual-outlined volumes with correlation coefficient of 0.98. CONCLUSIONS: The proposed method was shown to provide accurate segmentation for liver in the planning CT images where contrast agent is not applied. The authors' results also clearly demonstrated that the application of tracking the fuzzy borders could significantly reduce contour leakage during active contour evolution.

Potential of computer-aided diagnosis of high spectral and spatial resolution (HiSS) MRI in the classification of breast lesions.

PURPOSE: To compare the performance of computer-aided diagnosis (CADx) analysis of precontrast high spectral and spatial resolution (HiSS) MRI to that of clinical dynamic contrast-enhanced MRI (DCE-MRI) in the diagnostic classification of breast lesions. MATERIALS AND METHODS: Thirty-four malignant and seven benign lesions were scanned using two-dimensional (2D) HiSS and clinical 4D DCE-MRI protocols. Lesions were automatically segmented. Morphological features were calculated for HiSS, whereas both morphological and kinetic features were calculated for DCE-MRI. After stepwise feature selection, Bayesian artificial neural networks merged selected features, and receiver operating characteristic (ROC) analysis evaluated the performance with leave-one-lesion-out validation. RESULTS: AUC (area under the ROC curve) values of 0.92 ± 0.06 and 0.90 ± 0.05 were obtained using CADx on HiSS and DCE-MRI, respectively, in the task of classifying benign and malignant lesions. While we failed to show that the higher HiSS performance was significantly better than DCE-MRI, noninferiority testing confirmed that HiSS was not worse than DCE-MRI. CONCLUSION: CADx of HiSS (without contrast) performed similarly to CADx on clinical DCE-MRI; thus, computerized analysis of HiSS may provide sufficient information for diagnostic classification. The results are clinically important for patients in whom contrast agent is contra-indicated. Even in the limited acquisition mode of 2D single slice HiSS, by using quantitative image analysis to extract characteristics from the HiSS images, similar performance levels were obtained as compared with those from current clinical 4D DCE-MRI. As HiSS acquisitions become possible in 3D, CADx methods can also be applied. Because HiSS and DCE-MRI are based on different contrast mechanisms, the use of the two protocols in combination may increase diagnostic accuracy.

Feasibility study of in vivo MRI based dosimetric verification of proton end-of-range for liver cancer patients.

PURPOSE: To investigate the feasibility of using MRI to verify proton beam distal range for liver tumor treatment in a retrospective study. METHODS AND MATERIALS: Because the follow-up hepatocyte-specific functional MR imaging can detect the radiobiological change of liver tissue after radiation, we firstly registered the contrast-enhanced MR images to the planning CT images from 5 liver patients, then overlaid the prescribed dose distribution on the MR images. Since dose calculation is most accurate at the penumbra dose region, we correlated the MR signal intensity (SI) to the radiation dose at the superior/inferior penumbra region. This dose-SI correlation was finally employed on registered MR images to estimate the proton end-of-range. RESULTS: Statistically significant correlations between radiation dose and MR SI were observed in superior/inferior penumbra regions, with correlation coefficient ranging from 0.93 to 0.99. By applying the dose-SI correlation to the distal region of each proton beam, the mean difference between MR-estimated and the planned dose range was -2.18 ± 4.89 mm for anterior-posterior beams and -3.90 ± 5.87 mm for lateral beams. CONCLUSIONS: This feasibility study proved the principle that proton dose range can be verified in vivo by follow-up MR images after proton liver treatment.

Computerized three-class classification of MRI-based prognostic markers for breast cancer.

The purpose of this study is to investigate whether computerized analysis using three-class Bayesian artificial neural network (BANN) feature selection and classification can characterize tumor grades (grade 1, grade 2 and grade 3) of breast lesions for prognostic classification on DCE-MRI. A database of 26 IDC grade 1 lesions, 86 IDC grade 2 lesions and 58 IDC grade 3 lesions was collected. The computer automatically segmented the lesions, and kinetic and morphological lesion features were automatically extracted. The discrimination tasks-grade 1 versus grade 3, grade 2 versus grade 3, and grade 1 versus grade 2 lesions-were investigated. Step-wise feature selection was conducted by three-class BANNs. Classification was performed with three-class BANNs using leave-one-lesion-out cross-validation to yield computer-estimated probabilities of being grade 3 lesion, grade 2 lesion and grade 1 lesion. Two-class ROC analysis was used to evaluate the performances. We achieved AUC values of 0.80 ± 0.05, 0.78 ± 0.05 and 0.62 ± 0.05 for grade 1 versus grade 3, grade 1 versus grade 2, and grade 2 versus grade 3, respectively. This study shows the potential for (1) applying three-class BANN feature selection and classification to CADx and (2) expanding the role of DCE-MRI CADx from diagnostic to prognostic classification in distinguishing tumor grades.

Multimodality computer-aided breast cancer diagnosis with FFDM and DCE-MRI.

RATIONALE AND OBJECTIVES: To investigate a multimodality computer-aided diagnosis (CAD) scheme that combines image information from full-field digital mammography (FFDM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for computerized breast cancer classification. MATERIALS AND METHODS: From a retrospective FFDM database with 432 lesions (255 malignant, 177 benign) and a retrospective DCE-MRI database including 476 lesions (347 malignant, 129 benign), we constructed a multimodality dataset of 213 lesions (168 malignant, 45 benign). Each lesion was present on both FFDM and DCE-MRI images and deemed to be a difficult case given the necessity of having both clinical imaging exams. Using a manually indicated lesion location (ie, a seed point on FFDM images or a region of interest on DCE-MRI images, the computer automatically segmented the mass lesions and extracted lesion features). A subset of features was selected using linear stepwise feature selection and merged by a Bayesian artificial neural network to yield an estimate of the probability of malignancy. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of the selected features in distinguishing between malignant and benign lesions. RESULTS: With leave-one-lesion-out cross-validation on the multimodality dataset, the mammography-only features yielded an area under the ROC curve (AUC) of 0.74 +/- 0.04, and the DCE-MRI-only features yielded an AUC of 0.78 +/- 0.04. The combination of these two modalities, which included a spiculation feature from mammography and two kinetic features from DCE-MRI, yielded an AUC of 0.87 +/- 0.03. The improvement of combining multimodality information was statistically significant as compared to the use of single modality information alone. CONCLUSIONS: A CAD scheme that combines features extracted from FFDM and DCE-MRI images may be advantageous to single-modality CAD in the task of differentiating between malignant and benign lesions.

Exploring nonlinear feature space dimension reduction and data representation in breast Cadx with Laplacian eigenmaps and t-SNE.

PURPOSE: In this preliminary study, recently developed unsupervised nonlinear dimension reduction (DR) and data representation techniques were applied to computer-extracted breast lesion feature spaces across three separate imaging modalities: Ultrasound (U.S.) with 1126 cases, dynamic contrast enhanced magnetic resonance imaging with 356 cases, and full-field digital mammography with 245 cases. Two methods for nonlinear DR were explored: Laplacian eigenmaps [M. Belkin and P. Niyogi, "Laplacian eigenmaps for dimensionality reduction and data representation," Neural Comput. 15, 1373-1396 (2003)] and t-distributed stochastic neighbor embedding (t-SNE) [L. van der Maaten and G. Hinton, "Visualizing data using t-SNE," J. Mach. Learn. Res. 9, 2579-2605 (2008)]. METHODS: These methods attempt to map originally high dimensional feature spaces to more human interpretable lower dimensional spaces while preserving both local and global information. The properties of these methods as applied to breast computer-aided diagnosis (CADx) were evaluated in the context of malignancy classification performance as well as in the visual inspection of the sparseness within the two-dimensional and three-dimensional mappings. Classification performance was estimated by using the reduced dimension mapped feature output as input into both linear and nonlinear classifiers: Markov chain Monte Carlo based Bayesian artificial neural network (MCMC-BANN) and linear discriminant analysis. The new techniques were compared to previously developed breast CADx methodologies, including automatic relevance determination and linear stepwise (LSW) feature selection, as well as a linear DR method based on principal component analysis. Using ROC analysis and 0.632+bootstrap validation, 95% empirical confidence intervals were computed for the each classifier's AUC performance. RESULTS: In the large U.S. data set, sample high performance results include, AUC0.632+ = 0.88 with 95% empirical bootstrap interval [0.787;0.895] for 13 ARD selected features and AUC0.632+ = 0.87 with interval [0.817;0.906] for four LSW selected features compared to 4D t-SNE mapping (from the original 81D feature space) giving AUC0.632+ = 0.90 with interval [0.847;0.919], all using the MCMC-BANN. CONCLUSIONS: Preliminary results appear to indicate capability for the new methods to match or exceed classification performance of current advanced breast lesion CADx algorithms. While not appropriate as a complete replacement of feature selection in CADx problems, DR techniques offer a complementary approach, which can aid elucidation of additional properties associated with the data. Specifically, the new techniques were shown to possess the added benefit of delivering sparse lower dimensional representations for visual interpretation, revealing intricate data structure of the feature space.

Evaluation of computer-aided diagnosis on a large clinical full-field digital mammographic dataset.

RATIONALE AND OBJECTIVES: To convert and optimize our previously developed computerized analysis methods for use with images from full-field digital mammography (FFDM) for breast mass classification to aid in the diagnosis of breast cancer. MATERIALS AND METHODS: An institutional review board approved protocol was obtained, with waiver of consent for retrospective use of mammograms and pathology data. Seven hundred thirty-nine FFDM images, which contained 287 biopsy-proven breast mass lesions, of which 148 lesions were malignant and 139 lesions were benign, were retrospectively collected. Lesion margins were delineated by an expert breast radiologist and were used as the truth for lesion-segmentation evaluation. Our computerized image analysis method consisted of several steps: 1) identified lesions were automatically extracted from the parenchymal background using computerized segmentation methods; 2) a set of image characteristics (mathematic descriptors) were automatically extracted from image data of the lesions and surrounding tissues; and 3) selected features were merged into an estimate of the probability of malignancy using a Bayesian artificial neural network classifier. Performance of the analyses was evaluated at various stages of the conversion using receiver-operating characteristic analysis. RESULTS: An area under the curve value of 0.81 was obtained in the task of distinguishing between malignant and benign mass lesions in a round-robin by case evaluation on the entire FFDM dataset. We failed to show a statistically significant difference (P = .83) compared to results from our previous study in which the computerized classification was performed on digitized screen-film mammograms. CONCLUSIONS: Our computerized analysis methods developed on digitized screen-film mammography can be converted for use with FFDM. Results show that the computerized analysis methods for the diagnosis of breast mass lesions on FFDM are promising, and can potentially be used to aid clinicians in the diagnostic interpretation of FFDM.

Correlative feature analysis on FFDM.

Identifying the corresponding images of a lesion in different views is an essential step in improving the diagnostic ability of both radiologists and computer-aided diagnosis (CAD) systems. Because of the nonrigidity of the breasts and the 2D projective property of mammograms, this task is not trivial. In this pilot study, we present a computerized framework that differentiates between corresponding images of the same lesion in different views and noncorresponding images, i.e., images of different lesions. A dual-stage segmentation method, which employs an initial radial gradient index (RGI) based segmentation and an active contour model, is applied to extract mass lesions from the surrounding parenchyma. Then various lesion features are automatically extracted from each of the two views of each lesion to quantify the characteristics of density, size, texture and the neighborhood of the lesion, as well as its distance to the nipple. A two-step scheme is employed to estimate the probability that the two lesion images from different mammographic views are of the same physical lesion. In the first step, a correspondence metric for each pairwise feature is estimated by a Bayesian artificial neural network (BANN). Then, these pairwise correspondence metrics are combined using another BANN to yield an overall probability of correspondence. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of the individual features and the selected feature subset in the task of distinguishing corresponding pairs from noncorresponding pairs. Using a FFDM database with 123 corresponding image pairs and 82 noncorresponding pairs, the distance feature yielded an area under the ROC curve (AUC) of 0.81 +/- 0.02 with leave-one-out (by physical lesion) evaluation, and the feature metric subset, which included distance, gradient texture, and ROI-based correlation, yielded an AUC of 0.87 +/- 0.02. The improvement by using multiple feature metrics was statistically significant compared to single feature performance.

A dual-stage method for lesion segmentation on digital mammograms.

Mass lesion segmentation on mammograms is a challenging task since mass lesions are usually embedded and hidden in varying densities of parenchymal tissue structures. In this article, we present a method for automatic delineation of lesion boundaries on digital mammograms. This method utilizes a geometric active contour model that minimizes an energy function based on the homogeneities inside and outside of the evolving contour. Prior to the application of the active contour model, a radial gradient index (RGI)-based segmentation method is applied to yield an initial contour closer to the lesion boundary location in a computationally efficient manner. Based on the initial segmentation, an automatic background estimation method is applied to identify the effective circumstance of the lesion, and a dynamic stopping criterion is implemented to terminate the contour evolution when it reaches the lesion boundary. By using a full-field digital mammography database with 739 images, we quantitatively compare the proposed algorithm with a conventional region-growing method and an RGI-based algorithm by use of the area overlap ratio between computer segmentation and manual segmentation by an expert radiologist. At an overlap threshold of 0.4, 85% of the images are correctly segmented with the proposed method, while only 69% and 73% of the images are correctly delineated by our previous developed region-growing and RGI methods, respectively. This resulting improvement in segmentation is statistically significant.