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From telepathology to virtual pathology institution: the new world of digital pathology.

Telepathology has left its childhood. Its technical development is mature, and its use for primary (frozen section) and secondary (expert consultation) diagnosis has been expanded to a great amount. This is in contrast to a virtual pathology laboratory, which is still under technical constraints. Similar to telepathology, which can also be used for e-learning and e-training in pathology, as exemplarily is demonstrated on Digital Lung Pathology (Klaus.Kayser@charite.de) at least two kinds of virtual pathology laboratories will be implemented in the near future: a) those with distributed pathologists and distributed (> or = 1) laboratories associated to individual biopsy stations/surgical theatres, and b) distributed pathologists (usually situated in one institution) and a centralized laboratory, which digitizes complete histological slides. Both scenarios are under intensive technical investigations. The features of virtual pathology comprise a virtual pathology institution (mode a) that accepts a complete case with the patient's history, clinical findings, and (pre-selected) images for first diagnosis. The diagnostic responsibility is that of a conventional institution. The Internet serves as platform for information transfer, and an open server such as the iPATH (http://telepath.patho.unibas.ch) for coordination and performance of the diagnostic procedure. The size and number of transferred images have to be limited, and usual different magnifications have to be used. The sender needs to possess experiences in image sampling techniques, which present with the most significant information. A group of pathologists is "on duty", or selects one member for a predefined duty period. The diagnostic statement of the pathologist(s) on duty is retransmitted to the sender with full responsibility. The first experiences of a virtual pathology institution group working with the iPATH server working with a small hospital of the Salomon islands are promising. A centralized virtual pathology institution (mode b) depends upon the digitalization of a complete slide, and the transfer of large sized images to different pathologists working in one institution. The technical performance of complete slide digitalization is still under development. Virtual pathology can be combined with e-learning and e-training, that will serve for a powerful daily-work-integrated pathology system. At present, e-learning systems are "stand-alone" solutions distributed on CD or via Internet. A characteristic example is the Digital Lung Pathology CD, which includes about 60 different rare and common lung diseases with some features of electronic communication. These features include access to scientific library systems (PubMed), distant measurement servers (EuroQuant), automated immunohisto-chemistry measurements, or electronic journals (Elec J Pathol Histol, www.pathology-online.org). It combines e-learning and e-training with some acoustic support. A new and complete database based upon this CD will combine e-learning and e-teaching with the actual workflow in a virtual pathology institution (mode a). The technological problems are solved and do not depend upon technical constraints such as slide scanning systems. At present, telepathology serves as promoter for a complete new landscape in diagnostic pathology, the so-called virtual pathology institution. Industrial and scientific efforts will probably allow an implementation of this technique within the next two years with exciting diagnostic and scientific perspectives.

Computer Communication Networks↗

Digital pathology, image analysis, and artificial intelligence in liver disease.

Advances in digital pathology, image analysis, and artificial intelligence (AI) are rapidly transforming how pathologists and researchers interact with tissue samples and enable the development of diagnostic tools that harness high-resolution whole-slide images; these advances are in turn creating new opportunities for research, education, and routine clinical care globally. Liver disease is no exception, and digital pathology and AI have many applications in the diagnosis of liver cancer and liver diseases and in the assessment and management of transplantation. Although quantitative image analysis techniques have been applied to liver disease in research settings for over 50 years, recent improvements in image resolution, data storage, and the availability of advanced AI methods such as deep learning have driven multiple exciting developments. In this Review, we summarise the advancements in digital pathology, image analysis, and AI in liver disease. Key challenges such as access to and the logistics of using digital solutions, quality issues, and appropriate guidance in research and clinical use are reviewed, along with potential solutions to these challenges in the context of liver pathology and liver disease. Digital technologies are well established in liver pathology research, and access in clinical practice is increasing, with potential to address current laboratory challenges. Further evaluation is required to assess real-world effectiveness, clinical safety, and implementation of AI tools in liver pathology.

Journal Article↗

[Past, present and future of digital pathology].

The four main aspects of applied medical information technology, which change the traditional systems of the entire health service are signal and data processing, digital modelling and interface optimisation. The information technology serving individual clinical specialties including clinical histopathology is changing at each of the four levels resulting in transformation of the communication paradigms. The object of investigation in histopathology is the digital slide, which is accessible throughout the world with no time or geographical limits. It permits the digital modelling of routine histological and/or cytological slide and it also allows measurements by using image analysis or stereology software packages. The electronic slide can be viewed, examined and diagnosed on a computer connected to a microscope, a new interface in diagnostic histopathology. This study describes the main theoretical and practical aspects, including challenges, of digital pathology and it also discusses the conditions required for successful information management. It reviews the experiences of the last one and half decades gained in the field of pathological information technology in Hungary including its main episodes and milestones of development. Introducing its present state, this paper describes the concept and the mode of investigation of the digital slide. It shows the development and use of a virtual microscope in Hungary. Based on know-how including the British experience this review describes the possible uses of digital slides, which by improving communication could have a positive effect on the entire health care system. It summarises the possible and necessary components of a digital pathology laboratory, which may include the new Slide Archive and Communication System (SACS). Using experimental data it mentions the possibility of generating primary digital pathological sample and producing the so called optical biopsy with no need for removing tissue from the patient.

Analog-Digital Conversion↗

Storage and distribution of pathology digital images using integrated web-based viewing systems.

CONTEXT: Health care providers have expressed increasing interest in incorporating digital images of gross pathology specimens and photomicrographs in routine pathology reports. OBJECTIVE: To describe the multiple technical and logistical challenges involved in the integration of the various components needed for the development of a system for integrated Web-based viewing, storage, and distribution of digital images in a large health system. DESIGN: An Oracle version 8.1.6 database was developed to store, index, and deploy pathology digital photographs via our Intranet. The database allows for retrieval of images by patient demographics or by SNOMED code information. SETTING: The Intranet of a large health system accessible from multiple computers located within the medical center and at distant private physician offices. RESULTS: The images can be viewed using any of the workstations of the health system that have authorized access to our Intranet, using a standard browser or a browser configured with an external viewer or inexpensive plug-in software, such as Prizm 2.0. The images can be printed on paper or transferred to film using a digital film recorder. Digital images can also be displayed at pathology conferences by using wireless local area network (LAN) and secure remote technologies. CONCLUSIONS: The standardization of technologies and the adoption of a Web interface for all our computer systems allows us to distribute digital images from a pathology database to a potentially large group of users distributed in multiple locations throughout a large medical center.

Computer Storage Devices↗

Digital pathology and spatial omics in steatohepatitis: Clinical applications and discovery potentials.

Steatohepatitis with diverse etiologies is the most common histological manifestation in patients with liver disease. However, there are currently no specific histopathological features pathognomonic for metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, or metabolic dysfunction-associated steatotic liver disease with increased alcohol intake. Digitizing traditional pathology slides has created an emerging field of digital pathology, allowing for easier access, storage, sharing, and analysis of whole-slide images. Artificial intelligence (AI) algorithms have been developed for whole-slide images to enhance the accuracy and speed of the histological interpretation of steatohepatitis and are currently employed in biomarker development. Spatial biology is a novel field that enables investigators to map gene and protein expression within a specific region of interest on liver histological sections, examine disease heterogeneity within tissues, and understand the relationship between molecular changes and distinct tissue morphology. Here, we review the utility of digital pathology (using linear and nonlinear microscopy) augmented with AI analysis to improve the accuracy of histological interpretation. We will also discuss the spatial omics landscape with special emphasis on the strengths and limitations of established spatial transcriptomics and proteomics technologies and their application in steatohepatitis. We then highlight the power of multimodal integration of digital pathology augmented by machine learning (ML)algorithms with spatial biology. The review concludes with a discussion of the current gaps in knowledge, the limitations and premises of these tools and technologies, and the areas of future research.

Humans↗

New developments in digital pathology: from telepathology to virtual pathology laboratory.

AIMS: To analyse the present status and future development of computerized diagnostic pathology in terms of work-flow integrative telepathology and virtual laboratory. PRESENT STATUS: Telepathology has left its childhood. The technical development of telepathology is mature, in contrast to that of virtual pathology. Two kinds of virtual pathology laboratories are emerging: a) those with distributed pathologists and distributed (>=1) laboratories associated to individual biopsy stations/surgical theatres, and b) distributed pathologists working in a centralized laboratory. Both are under technical development. Telepathology can be used for e-learning and e-training in pathology, as exemplarily demonstrated on Digital Lung Pathology Pathology (www.pathology-online.org). FEATURES OF VIRTUAL PATHOLOGY: A virtual pathology institution (mode a) accepts a complete case with the patient's history, clinical findings, and (pre-selected) images for first diagnosis. The diagnostic responsibility is that of a conventional institution. The internet serves as platform for information transfer, and an open server such as the iPATH (http://telepath.patho.unibas.ch) for coordination and performance of the diagnostic procedure. The size of images has to be limited, and usual different magnifications have to be used. A group of pathologists is "on duty", or selects one member for a predefined duty period. The diagnostic statement of the pathologist(s) on duty is retransmitted to the sender with full responsibility. First experiences of a virtual pathology institution group working with the iPATH server (Dr. L. Banach, Dr. G. Haroske, Dr. I. Hurwitz, Dr. K. Kayser, Dr. K.D. Kunze, Dr. M. Oberholzer,) working with a small hospital of the Salomon islands are promising. A centralized virtual pathology institution (mode b) depends upon the digitalisation of a complete slide, and the transfer of large sized images to different pathologists working in one institution. The technical performance of complete slide digitalisation is still under development and does not completely fulfil the requirements of a conventional pathology institution at present. VIRTUAL PATHOLOGY AND E-LEARNING: At present, e-learning systems are "stand-alone" solutions distributed on CD or via internet. A characteristic example is the Digital Lung Pathology CD (www.pathology-online.org), which includes about 60 different rare and common lung diseases and internet access to scientific library systems (PubMed), distant measurement servers (EuroQuant), or electronic journals (Elec J Pathol Histol). A new and complete data base based upon this CD will combine e-learning and e-teaching with the actual workflow in a virtual pathology institution (mode a). The technological problems are solved and do not depend upon technical constraints such as slide scanning systems. PERSPECTIVES: Telepathology serves as promotor for a new landscape in diagnostic pathology, the so-called virtual pathology institution. Industrial and scientific efforts will probably allow an implementation of this technique within the next two years.

Artificial Intelligence↗

[Virtual microscopy and digital pathology].

Virtual microscopy has advanced considerably and is bound to be integrated into routine diagnostics in the very near future. Its integration into existing information systems builds up digital pathology. In this review, we present details, advantages and limitations of this novel technology and describe solutions regarding its adaptation to routine workflow. The chief aim is to define an uniform data format for virtual specimens to guarantee an interoperability between different systems. In the long term, digital archives and networks will be established that will allow for a worldwide access to virtual specimens.

Humans↗

The digital pathologies of chronic laminitis.

This review indicates that the patient-to-patient uniqueness commonly seen in chronic laminitis represents the variable presence of the digital pathologies. Although some degree of mechanical failure is always present, the secondary metabolic and growth dysplasias, vascular pathologies, and sepsis may or may not be evident. The presence and severity of these pathologies appear to have a more significant impact on the prognosis of individual cases than does the displacement of the distal phalanx. It should be reiterated that it is often the combined presence of these individual pathologies that gives rise to the patient that is totally refractory to treatment. In the absence of these pathologies, many horses with significant displacement of the distal phalanx are not in pain and are not in need of treatment. It thus follows that a key to the improved rehabilitation of difficult patients is focusing research on the physiopathology and diagnosis of these nonmechanical problems.

Animals↗

[Results of a series of transrectal ultrasound guided biopsy of the prostate in 6000 patients. Part I: pathology, digital rectal examination, transrectal ultrasound, and PSA].

OBJECTIVES: To analyze the results of transrectal ultrasound (TRUS) guided biopsy of the prostate in 6000 patients, and their relation to common-use clinical parameters. METHODS: We collected PSA, digital rectal examination, TRUS characteristics, and pathology report in a data- base including 6000 patients who underwent sextant TRUS biopsy from 1994 to December 2002. 861 of them underwent more than one biopsy, accounting for a total of 7127 biopsies. Sextant biopsy with samples from the most lateral portions of the prostate was the standard procedure so that they included peripheral zone only. We analyze pathological results and their relation with clinical variables. RESULTS: Total percentage of cancer in biopsy samples was 42.6%, with 39.1% in the first biopsy. Overall, repeated biopsies resulted in a 3.5% diagnostic yield increase. PIN or focal glandular atypia were detected in 2.0% and 2.1% of the cases respectively. The percentage of patients with Gleason score =<6 increased from 41.8% in the first biopsy to 70% in the third. Similarly, single core involvement increased from 21.% to 65%. Digital rectal examination and presence of hypoechogenic nodules specificity were 82.6 and 78.2% respectively. The incidence of prostate cancer with PSA between 4 and 10 ng/ml was 29.6%, 16.7% in those with PSA lower than 4 ng/ml. CONCLUSIONS: TRUS biopsy of the lateral prostatic areas offers a good diagnostic yield in comparison with most series of extensive biopsies. The sensitivity of TRUS has decreased but it maintains a high specificity which should not be forgotten when planning the TRUS strategy

Biopsy↗

Cancerous nuclei detection on digitized pathological lung color images.

In this paper, we propose a methodology (in the form of a software package) for automatic extraction of the cancerous nuclei in lung pathological color images. We first segment the images using an unsupervised Hopfield artificial neural network classifier and we label the segmented image based on chromaticity features and histogram analysis of the RGB color space components of the raw image. Then, we fill the holes inside the extracted nuclei regions based on the maximum drawable circle algorithm. All corrected nuclei regions are then classified into normal and cancerous using diagnostic rules formulated with respect to the rules used by experimented pathologist. The proposed method provides quantitative results in diagnosing a lung pathological image set of 16 cases that are comparable to an expert's diagnosis.

Adenocarcinoma↗

Digitized pathology: theory and experiences in automated tissue-based virtual diagnosis.

AIMS: To describe the theory and develop an automated virtual slide screening system. Theoretical considerations. Tissue-based diagnosis separates into (a) sampling procedure to allocate the slide area containing diagnostic information, and (b) evaluation of diagnosis from the selected area. Nyquist's theorem broadly applied in acoustics, serves to presetting the sampling accuracy. Tissue-based diagnosis relies on two different information systems: (a) texture, and (b) object information. Texture information can be derived by recursive formulas without image segmentation. Object information requires image segmentation and feature extraction. Both algorithms complete another to a "self-learning" classification system. METHODS: Non-overlapping compartments of the original virtual slide (image) are chosen at random with predefined error-rate (Nyquist's theorem). The standardized image compartments are subject for texture and object analysis. The recursive formula of texture analysis computes median gray values and local noise distribution. Object analysis includes automated measurements of immunohistochemically stained slides. The computations performed at different magnifications (x 2, x 4.5, x 10, x 20, x 40) are subject to multivariate statistically analysis and diagnosis classification. RESULTS: A total of 808 lung cancer cases of diagnoses groups: cohort (1) normal lung (318 cases) - cancer (490 cases); cancer subdivided: cohort (2) small cell lung cancer (10 cases) - non-small cell lung cancer (480 cases); non-small cell lung cancer subdivided: cohort (3) squamous cell carcinoma (318 cases) - adenocarcinoma (194 cases) - large cell carcinoma (70 cases) was analyzed. Cohorts (1) and (2) were classified correctly in 100%, cohort (3) in more than 95%. The selected area can be limited to 10% of the original image without increased error rate. A second approach included 233 breast tissue cases (105 normal, 128 breast carcinomas) and 88 lung tissue cases (58 normal, 38 cancer). Texture analysis revealed a correct classification with only 10 training set cases in >92% for both, breast and lung tissue. CONCLUSIONS: The developed system is a fast and reliable procedure to fulfill all requirements for an automated "pre-screening" of virtual slides in tissue-based diagnosis.

Algorithms↗

[Quantitative image analysis in pulmonary pathology - digitalization of preneoplastic lesions in human bronchial epithelium (author's transl)].

The report concerns the first phase of a quantitative study of normal and abnormal bronchial epithelium with the objective of establishing the digitalization of histologic patterns. Preparative methods, data collecting and handling, and further mathematical analysis are described. In cluster and discriminatory analysis the digitalized histologic features can be used to separate and classify the individual cases into the respective diagnostic groups.

Bronchi↗

The use of digital images in pathology.

Digital images are routinely used by the publishing industry, but most diagnostic pathologists are unfamiliar with the technology and its possibilities. This review aims to explain the basic principles of digital image acquisition, storage, manipulation and use, and the possibilities provided not only in research, but also in teaching and in routine diagnostic pathology. Images of natural objects are usually expressed digitally as 'bitmaps'--rectilinear arrays of small dots. The size of each dot can vary, but so can its information content in terms, for example, of colour, greyscale or opacity. Various file formats and compression algorithms are available. Video cameras connected to microscopes are familiar to most pathologists; video images can be converted directly to a digital form by a suitably equipped computer. Digital cameras and scanners are alternative acquisition tools of relevance to pathologists. Once acquired, a digital image can easily be subjected to the digital equivalent of any conventional darkroom manipulation and modern software allows much more flexibility, to such an extent that a new tool for scientific fraud has been created. For research, image enhancement and analysis is an increasingly powerful and affordable tool. Morphometric measurements are, after many predictions, at last beginning to be part of the toolkit of the diagnostic pathologist. In teaching, the potential to create dramatic yet informative presentations is demonstrated daily by the publishing industry; such methods are readily applicable to the classroom. The combination of digital images and the Internet raises many possibilities; for example, instead of seeking one expert diagnostic opinion, one could simultaneously seek the opinion of many, all around the globe. It is inevitable that in the coming years the use of digital images will spread from the laboratory to the medical curriculum and to the whole of diagnostic pathology.

Humans↗

Digital imaging applications in anatomic pathology.

Digital imaging has progressed at a rapid rate and is likely to eventually replace chemical photography in most areas of professional and amateur digital image acquisition. In pathology, digital microscopy has implications beyond that of taking a photograph. The arguments for adopting this new medium are compelling, and given similar developments in other areas of pathology and radiologic imaging, acceptance of the digital medium should be viewed as a component of the technological evolution of the laboratory. A digital image may be stored, replicated, catalogued, employed for educational purposes, transmitted for further interpretation (telepathology), analyzed for salient features (medical vision/image analysis), or form part of a wider digital healthcare strategy. Despite advances in digital camera technology, good image acquisition still requires good microscope optics and the correct calibration of all system components, something which many neglect. The future of digital imaging in pathology is very promising and new applications in the fields of automated quantification and interpretation are likely to have profound long-term influence on the practice of anatomic pathology. This paper discusses the state of the art of digital imaging in anatomic pathology.

Education, Medical↗