Nucleus segmentation: towards automated solutions.

Single nucleus segmentation is a frequent challenge of microscopy image processing, since it is the first step of many quantitative data analysis pipelines. The quality of tracking single cells, extracting features or classifying cellular phenotypes strongly depends on segmentation accuracy. Worldwide competitions have been held, aiming to improve segmentation, and recent years have definitely brought significant improvements: large annotated datasets are now freely available, several 2D segmentation strategies have been extended to 3D, and deep learning approaches have increased accuracy. However, even today, no generally accepted solution and benchmarking platform exist. We review the most recent single-cell segmentation tools, and provide an interactive method browser to select the most appropriate solution.

¡Estudiando el Desarrollo Embrionario y Fetal con el Microscopio Virtual! En Tiempos de Covid-19 / Studying Embryonic and Fetal Development with the Virtual Microscope! In the Times of Covid-19

RESUMEN: La Microscopía Virtual es una herramienta tecnológica que permite la visualización de imágenes digitales microscópicas de gran resolución a través de un computador imitando la funcionalidad de un microscopio óptico tradicional. El presente trabajo presenta nuestra experiencia en el uso de esta modalidad de trabajo, útil hoy en día, en medio de la pandemia por Covid-19.

SUMMARY: Virtual Microscopy is a technological tool that allows the visualization of high resolution microscopic digital images through a computer, imitating the functionality of a traditional light microscope. The present work presents our experience in the use of this working modality, useful today, in the midst of the Covid-19 pandemic.

Microcirculation in Cardiovascular Diseases.

Microcirculation is a system composed of interconnected microvessels, which is responsible for the distribution of oxygenated blood among and within organs according to regional metabolic demand. Critical medical conditions, e. g., sepsis, and heart failure are known triggers of microcirculatory disturbance, which usually develops early in such clinical pictures and represents an independent risk factor for mortality. Therefore, hemodynamic resuscitation aiming at restoring microcirculatory perfusion is of paramount importance. Until recently, however, resuscitation protocols were based on macrohemodynamic variables, which increases the risk of under or over resuscitation. The introduction of hand-held video-microscopy (HVM) into clinical practice has allowed real-time analysis of microcirculatory variables at the bedside and, hence, favored a more individualized approach. In the cardiac intensive care unit scenario, HVM provides essential information on patients' hemodynamic status, e. g., to classify the type of shock, to adequate the dosage of vasopressors or inotropes according to demand and define safer limits, to guide fluid therapy and red blood cell transfusion, to evaluate response to treatment, among others. Nevertheless, several drawbacks have to be addressed before HVM becomes a standard of care.

Smartphone-Based Device in Exotic Pet Medicine.

This article reviews the use of the smartphone in exotic pet medicine. The mobile app is the most instinctive use of the smartphone; however, there are very limited software dedicated to the exotic pet specifically. With an adapter, the smartphone can be attached to a regular endoscope and acts as a small endoscopic unit. Additional devices, such as infrared thermography or ultrasound, can be connected to the smartphone through the micro-USB port. The medical use of the smartphone is still in its infancy in veterinary medicine but can bring several solutions to the exotic pet practitioner and improve point-of-care evaluation.

Development of Functional Requirements for Ex Vivo Pathology Applications of In Vivo Microscopy Systems: A Proposal From the In Vivo Microscopy Committee of the College of American Pathologists.

CONTEXT.­: In vivo microscopy (IVM) allows direct, real-time visualization of tissue histology in living patients without the need for tissue removal, processing, or staining. The IVM technologies in clinical use include confocal microscopy and optical coherence tomography. These technologies also show promise for use with pathology specimens (ex vivo microscopy [EVM]). However, few systems designed for EVM are commercially available, at least in part because of the lack of defined minimal functional requirements (FRs). OBJECTIVE.­: To develop minimal FRs for likely high-volume pathology applications of EVM. DESIGN.­: The IVM Committee of the College of American Pathologists identified potential EVM pathology applications based on the published literature. A subcommittee of IVM and EVM early adopters and experts then defined FRs for the most likely EVM applications. RESULTS.­: Potential EVM applications include assessment of margins, adequacy of needle biopsies and aspirates for diagnosis, and transplant tissues; selection of tissue for molecular studies or biorepository; and guidance in block selection from gross specimens. The first 3 applications were selected for development of FRs. The FRs were identified based on existing laboratory practices and guidelines and input from experts in the field and included device footprint and portability, specimen preparation, imaging time, field of view or resolution, morphologic diagnostic capability, yield, accuracy, ease of use, safety, and cost. CONCLUSIONS.­: Consensus was achieved on FRs that would accommodate the selected EVM applications. Publication and dissemination of those FRs will provide guidance to engineers, researchers, and vendors on how to optimally adapt IVM technologies for EVM for widespread adoption by pathologists.

Beyond the microscope: interpreting renal biopsy findings in the era of precision medicine.

As rapid progress in science and biotechnology is affecting the practice of renal medicine, increasingly precise diagnostic assessment is needed to select the most effective therapeutic approach for individual patients. The kidney biopsy remains the gold standard for the diagnosis of renal disease, but the field of renal pathology is evolving, classification of renal parenchyma lesions and histopathological diagnostic criteria are undergoing more validation and updates, and new technologies and assays are sought to improve efficiency and accuracy of the diagnostic process. How new knowledge and scientific advances may potentially affect renal pathology is discussed.

Optimizing morphology through blood cell image analysis.

INTRODUCTION: Morphological review of the peripheral blood smear is still a crucial diagnostic aid as it provides relevant information related to the diagnosis and is important for selection of additional techniques. Nevertheless, the distinctive cytological characteristics of the blood cells are subjective and influenced by the reviewer's interpretation and, because of that, translating subjective morphological examination into objective parameters is a challenge. METHODS: The use of digital microscopy systems has been extended in the clinical laboratories. As automatic analyzers have some limitations for abnormal or neoplastic cell detection, it is interesting to identify quantitative features through digital image analysis for morphological characteristics of different cells. RESULT: Three main classes of features are used as follows: geometric, color, and texture. Geometric parameters (nucleus/cytoplasmic ratio, cellular area, nucleus perimeter, cytoplasmic profile, RBC proximity, and others) are familiar to pathologists, as they are related to the visual cell patterns. Different color spaces can be used to investigate the rich amount of information that color may offer to describe abnormal lymphoid or blast cells. Texture is related to spatial patterns of color or intensities, which can be visually detected and quantitatively represented using statistical tools. CONCLUSION: This study reviews current and new quantitative features, which can contribute to optimize morphology through blood cell digital image processing techniques.

Detecting and visualizing cell phenotype differences from microscopy images using transport-based morphometry.

Modern microscopic imaging devices are able to extract more information regarding the subcellular organization of different molecules and proteins than can be obtained by visual inspection. Predetermined numerical features (descriptors) often used to quantify cells extracted from these images have long been shown useful for discriminating cell populations (e.g., normal vs. diseased). Direct visual or biological interpretation of results obtained, however, is often not a trivial task. We describe an approach for detecting and visualizing phenotypic differences between classes of cells based on the theory of optimal mass transport. The method is completely automated, does not require the use of predefined numerical features, and at the same time allows for easily interpretable visualizations of the most significant differences. Using this method, we demonstrate that the distribution pattern of peripheral chromatin in the nuclei of cells extracted from liver and thyroid specimens is associated with malignancy. We also show the method can correctly recover biologically interpretable and statistically significant differences in translocation imaging assays in a completely automated fashion.

Microscopic imaging in endoscopy: endomicroscopy and endocytoscopy.

Performing real-time microscopy has been a vision of endoscopists since the very early phases of gastrointestinal endoscopy. Confocal endomicroscopy, an adaption of confocal laser scanning microscopy, and endocytoscopy, an adaption of white-light microscopy, have been introduced into the endoscopic armamentarium in the past decade. Both techniques yield on-site histological information. Multiple trials have demonstrated the ability of gastroenterologists to obtain and interpret microscopic images from the upper and lower gastrointestinal tract, and also the hepatobiliary-pancreatic system, during endoscopy. Such microscopic information has been successfully used in expert hands to minimize sampling error by 'smart', microscopically targeted biopsies and to guide endoscopic interventions. However, endomicroscopy is also unique in its ability to dynamically visualize cellular processes in their native environment free of artefacts. This ability enables fundamental insights into mechanisms of human diseases in clinical and translational science.

[Impact of the pathology in modern medicine]. / Représentation en sciences du vivant (9) émergence d'une spécialité médicale nouvelle : la pathologie.

In this review, the authors emphasize the pivotal role of the pathology in the setting of a revolution which progressively transforms medical sciences into basic sciences. Several key aspects of this specialty will be discussed together with the main perspectives in the fields of oncologic disorders.

Classifications of lymphoma; reflections of time and technology.

'Nowhere in pathology has a chaos of names so clouded clear concepts as in the subject lymphoid tumors'. R.A. Willis. In 1858, Rudolf Virchow, with a primitive microscope and limited experiential base, recognized 'at least three different conditions here, hyperinosis, leucocytosis and leukemia….'. One hundred and fifty years later, the World Health Organization (WHO 2008), with a much more extensive armamentarium of tools, and a wealth of diverse experience, promulgated criteria distinguishing more than 100 types of 'Tumors of the Hematopoietic and Lymphoid Tissues'. From three to one hundred and three; this is progress! And this is history! Our goal is to examine the course and causes of this history; how we moved from three entities to a hundred and three, what we have learned from it, and how we may use the insights that we have gained to anticipate 'future histories' in this marvelously dynamic area of biology and disease.