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

Ki67 nuclei detection and ki67-index estimation: A novel automatic approach based on human vision modeling

Background: The protein ki67 (pki67) is a marker of tumor aggressiveness, and its expression has been proven to be useful in the prognostic and predictive evaluation of several types of tumors. To numerically quantify the pki67 presence in cancerous tissue areas, pathologists generally analyze histochemical images to count the number of tumor nuclei marked for pki67. This allows estimating the ki67-index, that is the percentage of tumor nuclei positive for pki67 over all the tumor nuclei. Given the high image resolution and dimensions, its estimation by expert clinicians is particularly laborious and time consuming. Though automatic cell counting techniques have been presented so far, the problem is still open. Results: In this paper we present a novel automatic approach for the estimations of the ki67-index. The method starts by exploiting the STRESS algorithm to produce a color enhanced image where all pixels belonging to nuclei are easily identified by thresholding, and then separated into positive (i.e. pixels belonging to nuclei marked for pki67) and negative by a binary classification tree. Next, positive and negative nuclei pixels are processed separately by two multiscale procedures identifying isolated nuclei and separating adjoining nuclei. The multiscale procedures exploit two Bayesian classification trees to recognize positive and negative nuclei-shaped regions. Conclusions: The evaluation of the computed results, both through experts' visual assessments and through the comparison of the computed indexes with those of experts, proved that the prototype is promising, so that experts believe in its potential as a tool to be exploited in the clinical practice as a valid aid for clinicians estimating the ki67-index. The MATLAB source code is open source for research purposes

Automated Identification of Cell Type Specific Genes in the Mouse Brain by Image Computing of Expression Patterns

Background: Differential gene expression patterns in cells of the mammalian brain result in the morphological, connectional, and functional diversity of cells. A wide variety of studies have shown that certain genes are expressed only in specific cell-types. Analysis of cell-type-specific gene expression patterns can provide insights into the relationship between genes, connectivity, brain regions, and cell-types. However, automated methods for identifying cell-type-specific genes are lacking to date. Results: Here, we describe a set of computational methods for identifying cell-type-specific genes in the mouse brain by automated image computing of in situ hybridization (ISH) expression patterns. We applied invariant image feature descriptors to capture local gene expression information from cellular-resolution ISH images. We then built image-level representations by applying vector quantization on the image descriptors. We employed regularized learning methods for classifying genes specifically expressed in different brain cell-types. These methods can also rank image features based on their discriminative power. We used a data set of 2,872 genes from the Allen Brain Atlas in the experiments. Results showed that our methods are predictive of cell-type-specificity of genes. Our classifiers achieved AUC values of approximately 87% when the enrichment level is set to 20. In addition, we showed that the highly-ranked image features captured the relationship between cell-types. Conclusions: Overall, our results showed that automated image computing methods could potentially be used to identify cell-type-specific genes in the mouse brain

VIDEO FOREGROUND LOCALIZATION FROM TRADITIONAL METHODS TO DEEP LEARNING

These days, detection of Visual Attention Regions (VAR), such as moving objects has become an integral part of many Computer Vision applications, viz. pattern recognition, object detection and classification, video surveillance, autonomous driving, human-machine interaction (HMI), and so forth. The moving object identification using bounding boxes has matured to the level of localizing the objects along their rigid borders and the process is called foreground localization (FGL). Over the decades, many image segmentation methodologies have been well studied, devised, and extended to suit the video FGL. Despite that, still, the problem of video foreground (FG) segmentation remains an intriguing task yet appealing due to its ill-posed nature and myriad of applications. Maintaining spatial and temporal coherence, particularly at object boundaries, persists challenging, and computationally burdensome. It even gets harder when the background possesses dynamic nature, like swaying tree branches or shimmering water body, and illumination variations, shadows cast by the moving objects, or when the video sequences have jittery frames caused by vibrating or unstable camera mounts on a surveillance post or moving robot. At the same time, in the analysis of traffic flow or human activity, the performance of an intelligent system substantially depends on its robustness of localizing the VAR, i.e., the FG. To this end, the natural question arises as what is the best way to deal with these challenges? Thus, the goal of this thesis is to investigate plausible real-time performant implementations from traditional approaches to modern-day deep learning (DL) models for FGL that can be applicable to many video content-aware applications (VCAA). It focuses mainly on improving existing methodologies through harnessing multimodal spatial and temporal cues for a delineated FGL. The first part of the dissertation is dedicated for enhancing conventional sample-based and Gaussian mixture model (GMM)-based video FGL using probability mass function (PMF), temporal median filtering, and fusing CIEDE2000 color similarity, color distortion, and illumination measures, and picking an appropriate adaptive threshold to extract the FG pixels. The subjective and objective evaluations are done to show the improvements over a number of similar conventional methods. The second part of the thesis focuses on exploiting and improving deep convolutional neural networks (DCNN) for the problem as mentioned earlier. Consequently, three models akin to encoder-decoder (EnDec) network are implemented with various innovative strategies to improve the quality of the FG segmentation. The strategies are not limited to double encoding - slow decoding feature learning, multi-view receptive field feature fusion, and incorporating spatiotemporal cues through long-shortterm memory (LSTM) units both in the subsampling and upsampling subnetworks. Experimental studies are carried out thoroughly on all conditions from baselines to challenging video sequences to prove the effectiveness of the proposed DCNNs. The analysis demonstrates that the architectural efficiency over other methods while quantitative and qualitative experiments show the competitive performance of the proposed models compared to the state-of-the-art