Novel image markers for non-small cell lung cancer classification and survival prediction

BACKGROUND: Non-small cell lung cancer (NSCLC), the most common type of lung cancer, is one of serious diseases causing death for both men and women. Computer-aided diagnosis and survival prediction of NSCLC, is of great importance in providing assistance to diagnosis and personalize therapy planning for lung cancer patients. RESULTS: In this paper we have proposed an integrated framework for NSCLC computer-aided diagnosis and survival analysis using novel image markers. The entire biomedical imaging informatics framework consists of cell detection, segmentation, classification, discovery of image markers, and survival analysis. A robust seed detection-guided cell segmentation algorithm is proposed to accurately segment each individual cell in digital images. Based on cell segmentation results, a set of extensive cellular morphological features are extracted using efficient feature descriptors. Next, eight different classification techniques that can handle high-dimensional data have been evaluated and then compared for computer-aided diagnosis. The results show that the random forest and adaboost offer the best classification performance for NSCLC. Finally, a Cox proportional hazards model is fitted by component-wise likelihood based boosting. Significant image markers have been discovered using the bootstrap analysis and the survival prediction performance of the model is also evaluated. CONCLUSIONS: The proposed model have been applied to a lung cancer dataset that contains 122 cases with complete clinical information. The classification performance exhibits high correlations between the discovered image markers and the subtypes of NSCLC. The survival analysis demonstrates strong prediction power of the statistical model built from the discovered image markers

Novel Image Markers for Non-Small Cell Lung Cancer Classification and Survival Prediction

BACKGROUND: Non-small cell lung cancer (NSCLC), the most common type of lung cancer, is one of serious diseases causing death for both men and women. Computer-aided diagnosis and survival prediction of NSCLC, is of great importance in providing assistance to diagnosis and personalize therapy planning for lung cancer patients. RESULTS: In this paper we have proposed an integrated framework for NSCLC computer-aided diagnosis and survival analysis using novel image markers. The entire biomedical imaging informatics framework consists of cell detection, segmentation, classification, discovery of image markers, and survival analysis. A robust seed detection-guided cell segmentation algorithm is proposed to accurately segment each individual cell in digital images. Based on cell segmentation results, a set of extensive cellular morphological features are extracted using efficient feature descriptors. Next, eight different classification techniques that can handle high-dimensional data have been evaluated and then compared for computer-aided diagnosis. The results show that the random forest and adaboost offer the best classification performance for NSCLC. Finally, a Cox proportional hazards model is fitted by component-wise likelihood based boosting. Significant image markers have been discovered using the bootstrap analysis and the survival prediction performance of the model is also evaluated. CONCLUSIONS: The proposed model have been applied to a lung cancer dataset that contains 122 cases with complete clinical information. The classification performance exhibits high correlations between the discovered image markers and the subtypes of NSCLC. The survival analysis demonstrates strong prediction power of the statistical model built from the discovered image markers

An empirical evaluation of nuclei segmentation from H&E images in a real application scenario

Cell nuclei segmentation is a challenging task, especially in real applications, when the target images significantly differ between them. This task is also challenging for methods based on convolutional neural networks (CNNs), which have recently boosted the performance of cell nuclei segmentation systems. However, when training data are scarce or not representative of deployment scenarios, they may suffer from overfitting to a different extent, and may hardly generalise to images that differ from the ones used for training. In this work, we focus on real-world, challenging application scenarios when no annotated images from a given dataset are available, or when few images (even unlabelled) of the same domain are available to perform domain adaptation. To simulate this scenario, we performed extensive cross-dataset experiments on several CNN-based state-of-the-art cell nuclei segmentation methods. Our results show that some of the existing CNN-based approaches are capable of generalising to target images which resemble the ones used for training. In contrast, their effectiveness considerably degrades when target and source significantly differ in colours and scale

Nuclei Detection Using Mixture Density Networks

Nuclei detection is an important task in the histology domain as it is a main step toward further analysis such as cell counting, cell segmentation, study of cell connections, etc. This is a challenging task due to the complex texture of histology image, variation in shape, and touching cells. To tackle these hurdles, many approaches have been proposed in the literature where deep learning methods stand on top in terms of performance. Hence, in this paper, we propose a novel framework for nuclei detection based on Mixture Density Networks (MDNs). These networks are suitable to map a single input to several possible outputs and we utilize this property to detect multiple seeds in a single image patch. A new modified form of a cost function is proposed for training and handling patches with missing nuclei. The probability maps of the nuclei in the individual patches are next combined to generate the final image-wide result. The experimental results show the state-of-the-art performance on complex colorectal adenocarcinoma dataset.Comment: 8 pages, 3 figure

Nuclei/Cell Detection in Microscopic Skeletal Muscle Fiber Images and Histopathological Brain Tumor Images Using Sparse Optimizations

Nuclei/Cell detection is usually a prerequisite procedure in many computer-aided biomedical image analysis tasks. In this thesis we propose two automatic nuclei/cell detection frameworks. One is for nuclei detection in skeletal muscle fiber images and the other is for brain tumor histopathological images. For skeletal muscle fiber images, the major challenges include: i) shape and size variations of the nuclei, ii) overlapping nuclear clumps, and iii) a series of z-stack images with out-of-focus regions. We propose a novel automatic detection algorithm consisting of the following components: 1) The original z-stack images are first converted into one all-in-focus image. 2) A sufficient number of hypothetical ellipses are then generated for each nuclei contour. 3) Next, a set of representative training samples and discriminative features are selected by a two-stage sparse model. 4) A classifier is trained using the refined training data. 5) Final nuclei detection is obtained by mean-shift clustering based on inner distance. The proposed method was tested on a set of images containing over 1500 nuclei. The results outperform the current state-of-the-art approaches. For brain tumor histopathological images, the major challenges are to handle significant variations in cell appearance and to split touching cells. The proposed novel automatic cell detection consists of: 1) Sparse reconstruction for splitting touching cells. 2) Adaptive dictionary learning for handling cell appearance variations. The proposed method was extensively tested on a data set with over 2000 cells. The result outperforms other state-of-the-art algorithms with F1 score = 0.96

Automatic segmentation of overlapping cervical smear cells based on local distinctive features and guided shape deformation

Automated segmentation of cells from cervical smears poses great challenge to biomedical image analysis because of the noisy and complex background, poor cytoplasmic contrast and the presence of fuzzy and overlapping cells. In this paper, we propose an automated segmentation method for the nucleus and cytoplasm in a cluster of cervical cells based on distinctive local features and guided sparse shape deformation. Our proposed approach is performed in two stages: segmentation of nuclei and cellular clusters, and segmentation of overlapping cytoplasm. In the rst stage, a set of local discriminative shape and appearance cues of image superpixels is incorporated and classi ed by the Support Vector Machine (SVM) to segment the image into nuclei, cellular clusters, and background. In the second stage, a robust shape deformation framework is proposed, based on Sparse Coding (SC) theory and guided by representative shape features, to construct the cytoplasmic shape of each overlapping cell. Then, the obtained shape is re ned by the Distance Regularized Level Set Evolution (DRLSE) model. We evaluated our approach using the ISBI 2014 challenge dataset, which has 135 synthetic cell images for a total of 810 cells. Our results show that our approach outperformed existing approaches in segmenting overlapping cells and obtaining accurate nuclear boundaries. Keywords: overlapping cervical smear cells, feature extraction, sparse coding, shape deformation, distance regularized level set

Tumor cell load and heterogeneity estimation from diffusion-weighted MRI calibrated with histological data: an example from lung cancer

Producción CientíficaDiffusion-weighted magnetic resonance imaging (DWI) is a key non-invasive imaging technique for cancer diagnosis and tumor treatment assessment, reflecting Brownian movement of water molecules in tissues. Since densely packed cells restrict molecule mobility, tumor tissues produce usually higher signal (a.k.a. less attenuated signal) on isotropic maps compared with normal tissues. However, no general quantitative relation between DWI data and the cell density has been established. In order to link low-resolution clinical cross-sectional data with high-resolution histological information, we developed an image processing and analysis chain, which was used to study the correlation between the diffusion coefficient (D value) estimated from DWI and tumor cellularity from serial histological slides of a resected non-small cell lung cancer tumor. Color deconvolution followed by cell nuclei segmentation was performed on digitized histological images to determine local and cell-type specific 2d (two-dimensional) densities. From these, the 3d cell density was inferred by a model-based sampling technique, which is necessary for the calculation of local and global 3d tumor cell count. Next, DWI sequence information was overlaid with high-resolution CT data and the resected histology using prominent anatomical hallmarks for co-registration of histology tissue blocks and non-invasive imaging modalities' data. The integration of cell numbers information and DWI data derived from different tumor areas revealed a clear negative correlation between cell density and D value. Importantly, spatial tumor cell density can be calculated based on DWI data. In summary, our results demonstrate that tumor cell count and heterogeneity can be predicted from DWI data, which may open new opportunities for personalized diagnosis and therapy optimization

Conceptual data sampling for breast cancer histology image classification

Data analytics have become increasingly complicated as the amount of data has increased. One technique that is used to enable data analytics in large datasets is data sampling, in which a portion of the data is selected to preserve the data characteristics for use in data analytics. In this paper, we introduce a novel data sampling technique that is rooted in formal concept analysis theory. This technique is used to create samples reliant on the data distribution across a set of binary patterns. The proposed sampling technique is applied in classifying the regions of breast cancer histology images as malignant or benign. The performance of our method is compared to other classical sampling methods. The results indicate that our method is efficient and generates an illustrative sample of small size. It is also competing with other sampling methods in terms of sample size and sample quality represented in classification accuracy and F1 measure