Nuclei & Glands Instance Segmentation in Histology Images: A Narrative Review

Instance segmentation of nuclei and glands in the histology images is an important step in computational pathology workflow for cancer diagnosis, treatment planning and survival analysis. With the advent of modern hardware, the recent availability of large-scale quality public datasets and the community organized grand challenges have seen a surge in automated methods focusing on domain specific challenges, which is pivotal for technology advancements and clinical translation. In this survey, 126 papers illustrating the AI based methods for nuclei and glands instance segmentation published in the last five years (2017-2022) are deeply analyzed, the limitations of current approaches and the open challenges are discussed. Moreover, the potential future research direction is presented and the contribution of state-of-the-art methods is summarized. Further, a generalized summary of publicly available datasets and a detailed insights on the grand challenges illustrating the top performing methods specific to each challenge is also provided. Besides, we intended to give the reader current state of existing research and pointers to the future directions in developing methods that can be used in clinical practice enabling improved diagnosis, grading, prognosis, and treatment planning of cancer. To the best of our knowledge, no previous work has reviewed the instance segmentation in histology images focusing towards this direction.Comment: 60 pages, 14 figure

In vitro quantitative imaging assay for phagocytosis of dad neuroblastoma cells by iPSC-macrophages

Microglia orchestrate neuroimmune responses in several neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Microglia clear up dead and dying neurons through the process of efferocytosis, a specialized form of phagocytosis. The phagocytosis function can be disrupted by environmental or genetic risk factors that affect microglia. This paper presents a rapid and simple in vitro microscopy protocol for studying microglial efferocytosis in an induced pluripotent stem cell (iPSC) model of microglia, using a human neuroblastoma cell line (SH-SY5Y) labeled with a pH-sensitive dye for the phagocytic cargo. The procedure results in a high yield of dead neuroblastoma cells, which display surface phosphatidylserine, recognized as an "eat-me" signal by phagocytes. The 96-well plate assay is suitable for live-cell time-lapse imaging, or the plate can be successfully fixed prior to further processing and quantified by high-content microscopy. Fixed-cell high-content microscopy enables the assay to be scaled up for screening of small molecule inhibitors or assessing the phagocytic function of genetic variant iPSC lines. While this assay was developed to study phagocytosis of whole dead neuroblastoma cells by iPSC-macrophages, the assay can be easily adapted for other cargoes relevant to neurodegenerative diseases, such as synaptosomes and myelin, and other phagocytic cell types

Accelerating Sensitivity Analysis in Microscopy Image Segmentation Workflows

With the increasingly availability of digital microscopy imagery equipments there is a demand for efficient execution of whole slide tissue image applications. Through the process of sensitivity analysis it is possible to improve the output quality of such applications, and thus, improve the desired analysis quality. Due to the high computational cost of such analyses and the recurrent nature of executed tasks from sensitivity analysis methods (i.e., reexecution of tasks), the opportunity for computation reuse arises. By performing computation reuse we can optimize the run time of sensitivity analysis applications. This work focuses then on finding new ways to take advantage of computation reuse opportunities on multiple task abstraction levels. This is done by presenting the coarse-grain merging strategy and the new fine-grain merging algorithms, implemented on top of the Region Templates Framework.Comment: 44 page

Computer aided diagnosis algorithms for digital microscopy

Automatic analysis and information extraction from an image is still a highly chal- lenging research problem in the computer vision area, attempting to describe the image content with computational and mathematical techniques. Moreover the in- formation extracted from the image should be meaningful and as most discrimi- natory as possible, since it will be used to categorize its content according to the analysed problem. In the Medical Imaging domain this issue is even more felt because many important decisions that affect the patient care, depend on the use- fulness of the information extracted from the image. Manage medical image is even more complicated not only due to the importance of the problem, but also because it needs a fair amount of prior medical knowledge to be able to represent with data the visual information to which pathologist refer. Today medical decisions that impact patient care rely on the results of laboratory tests to a greater extent than ever before, due to the marked expansion in the number and complexity of offered tests. These developments promise to improve the care of patients, but the more increase the number and complexity of the tests, the more increases the possibility to misapply and misinterpret the test themselves, leading to inappropriate diagnosis and therapies. Moreover, with the increased number of tests also the amount of data to be analysed increases, forcing pathologists to devote much time to the analysis of the tests themselves rather than to patient care and the prescription of the right therapy, especially considering that most of the tests performed are just check up tests and most of the analysed samples come from healthy patients. Then, a quantitative evaluation of medical images is really essential to overcome uncertainty and subjectivity, but also to greatly reduce the amount of data and the timing for the analysis. In the last few years, many computer assisted diagno- sis systems have been developed, attempting to mimic pathologists by extracting features from the images. Image analysis involves complex algorithms to identify and characterize cells or tissues using image pattern recognition technology. This thesis addresses the main problems associated to the digital microscopy analysis in histology and haematology diagnosis, with the development of algorithms for the extraction of useful information from different digital images, but able to distinguish different biological structures in the images themselves. The proposed methods not only aim to improve the degree of accuracy of the analysis, and reducing time, if used as the only means of diagnoses, but also they can be used as intermediate tools for skimming the number of samples to be analysed directly from the pathologist, or as double check systems to verify the correct results of the automated facilities used today