Large-scale computations on histology images reveal grade-differentiating parameters for breast cancer

BACKGROUND: Tumor classification is inexact and largely dependent on the qualitative pathological examination of the images of the tumor tissue slides. In this study, our aim was to develop an automated computational method to classify Hematoxylin and Eosin (H&E) stained tissue sections based on cancer tissue texture features. METHODS: Image processing of histology slide images was used to detect and identify adipose tissue, extracellular matrix, morphologically distinct cell nuclei types, and the tubular architecture. The texture parameters derived from image analysis were then applied to classify images in a supervised classification scheme using histologic grade of a testing set as guidance. RESULTS: The histologic grade assigned by pathologists to invasive breast carcinoma images strongly correlated with both the presence and extent of cell nuclei with dispersed chromatin and the architecture, specifically the extent of presence of tubular cross sections. The two parameters that differentiated tumor grade found in this study were (1) the number density of cell nuclei with dispersed chromatin and (2) the number density of tubular cross sections identified through image processing as white blobs that were surrounded by a continuous string of cell nuclei. Classification based on subdivisions of a whole slide image containing a high concentration of cancer cell nuclei consistently agreed with the grade classification of the entire slide. CONCLUSION: The automated image analysis and classification presented in this study demonstrate the feasibility of developing clinically relevant classification of histology images based on micro- texture. This method provides pathologists an invaluable quantitative tool for evaluation of the components of the Nottingham system for breast tumor grading and avoid intra-observer variability thus increasing the consistency of the decision-making process

Coupled Analysis of In Vitro and Histology Tissue Samples to Quantify Structure-Function Relationship

The structure/function relationship is fundamental to our understanding of biological systems at all levels, and drives most, if not all, techniques for detecting, diagnosing, and treating disease. However, at the tissue level of biological complexity we encounter a gap in the structure/function relationship: having accumulated an extraordinary amount of detailed information about biological tissues at the cellular and subcellular level, we cannot assemble it in a way that explains the correspondingly complex biological functions these structures perform. To help close this information gap we define here several quantitative temperospatial features that link tissue structure to its corresponding biological function. Both histological images of human tissue samples and fluorescence images of three-dimensional cultures of human cells are used to compare the accuracy of in vitro culture models with their corresponding human tissues. To the best of our knowledge, there is no prior work on a quantitative comparison of histology and in vitro samples. Features are calculated from graph theoretical representations of tissue structures and the data are analyzed in the form of matrices and higher-order tensors using matrix and tensor factorization methods, with a goal of differentiating between cancerous and healthy states of brain, breast, and bone tissues. We also show that our techniques can differentiate between the structural organization of native tissues and their corresponding in vitro engineered cell culture models

Constrained distance transforms for spatial atlas registration

BACKGROUND: Spatial frameworks are used to capture organ or whole organism image data in biomedical research. The registration of large biomedical volumetric images is a complex and challenging task, but one that is required for spatially mapped biomedical atlas systems. In most biomedical applications the transforms required are non-rigid and may involve significant deformation relating to variation in pose, natural variation and mutation. Here we develop a new technique to establish such transformations for mapping data that cannot be achieved by existing approaches and that can be used interactively for expert editorial review. RESULTS: This paper presents the Constrained Distance Transform (CDT), a novel method for interactive image registration. The CDT uses radial basis function transforms with distances constrained to geodesics within the domains of the objects being registered. A geodesic distance algorithm is discussed and evaluated. Examples of registration using the CDT are presented. CONCLUSION: The CDT method is shown to be capable of simultaneous registration and foreground segmentation even when very large deformations are required

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Computer assisted detection of breast lesions in magnetic resonance images

Nowadays preventive screening policies and increased awareness initiatives are up surging the workload of radiologists. Due to the growing number of women undergoing first-level screening tests, systems that can make these operations faster and more effective are required. This paper presents a Computer Assisted Detection system based on medical imaging techniques and capable of labeling potentially cancerous breast lesions. This work is based on MRIs performed with morphological and dynamic sequences, obtained and classified thanks to the collaboration of the specialists from the University of Bari Aldo Moro (Italy). A first set of 60 images was acquired without Contrast Method for each patient and, subsequently, 100 more slices were taken with Contrast Method. This article formally describes the techniques adopted to segment these images and extract the most significant features from each Region of Interest (ROI). Then, the underlying architecture of the suggested Artificial Neural Network (ANN) responsible of identifying suspect lesions will be presented. We will discuss the architecture of the supervised neural network based on the algorithm named Robust Error Back Propagation, trained and optimized so to maximize the number of True Positive ROIs, i.e., the actual tumor regions. The training set, built with physicians’ help, consists of 94 lesions and 3700 regions of any interest extracted with the proposed segmentation technique. Performances of the ANN, trained using 60% of the samples, are evaluated in terms of accuracy, sensitivity and specificity indices. In conclusion, these tests show that a supervised machine learning approach to the detection of breast lesions in Magnetic Resonance Images is consistent, and shows good performance, especially from a False Negative reduction perspective

How good a shallow neural network is for solving non-linear decision-making problems

The universe approximate theorem states that a shallow neural network (one hidden layer) can represent any non-linear function. In this paper, we aim at examining how good a shallow neural network is for solving non-linear decision making problems. We proposed a performance driven incremental approach to searching the best shallow neural network for decision making, given a data set. The experimental results on the two benchmark data sets, Breast Cancer in Wisconsin and SMS Spams, demonstrate the correction of universe approximate theorem, and show that the number of hidden neurons, taking about the half of input number, is good enough to represent the function from data. It is shown that the performance driven BP learning is faster than the error-driven BP learning, and that the performance of the SNN obtained by the former is not worse than that of the SNN obtained by the latter. This indicates that when learning a neural network with the BP algorithm, the performance reaches a certain value quickly, but the error may still keep reducing. The performance of the SNNs for the two databases is comparable to or better than that of the optimal linguistic attribute hierarchy, obtained by a genetic algorithm in wrapper or in terms of semantics manually, which is much time-consuming