How to measure diagnosis-associated information in virtual slides

The distribution of diagnosis-associated information in histological slides is often spatial dependent. A reliable selection of the slide areas containing the most significant information to deriving the associated diagnosis is a major task in virtual microscopy. Three different algorithms can be used to select the appropriate fields of view: 1) Object dependent segmentation combined with graph theory; 2) time series associated texture analysis; and 3) geometrical statistics based upon geometrical primitives. These methods can be applied by sliding technique (i.e., field of view selection with fixed frames), and by cluster analysis. The implementation of these methods requires a standardization of images in terms of vignette correction and gray value distribution as well as determination of appropriate magnification (method 1 only). A principle component analysis of the color space can significantly reduce the necessary computation time. Method 3 is based upon gray value dependent segmentation followed by graph theory application using the construction of (associated) minimum spanning tree and Voronoi’s neighbourhood condition. The three methods have been applied on large sets of histological images comprising different organs (colon, lung, pleura, stomach, thyroid) and different magnifications, The trials resulted in a reproducible and correct selection of fields of view in all three methods. The different algorithms can be combined to a basic technique of field of view selection, and a general theory of “image information” can be derived. The advantages and constraints of the applied methods will be discussed

Specificities of Electronic Publication in Medicine

Background Electronic Media are considered to be a useful tool to distribute scientific information in medicine. Starting in this century all main publishers use electronic information transfer and distribution, either solely by electronic media or in combination with conventional paper printing. Theory Information distribution and communication require a sender (author), a transport medium (visual or acoustic signals, telephone, radio, TV, printed journals), and a receiver (hearer, reader). Information distribution in science and medicine should permit an objective and non-biased understanding of the transferred information by the receiver (doctor). These actions should be repeatable in time and space. This aim is in contrast to emotional, business-oriented, or political information transfer that commonly wants to direct the receiver in a certain surge or emotion. Implementation Scientific, peer reviewed open access journals have been established since the beginning of this century. After a period of hesitation and resistance which lasted for about 10 years, now-a-days nearly all big publishing companies offer open access journals in their product line. Most of them still hold on paper printed journals in addition, others offer hybrid journals, i.e., paper printed information display contemporary with electronic distribution. The electronic structures differ from classic structures (different, subject oriented domains) to articles of different focus that are fully integrated in only one individual domain. The advantages and disadvantages of the different structures are discussed in detail. Conclusions and perspectives Information distribution and communication is one important issue of life. The progress of technology does not stop at the doors of research and practice in medicine. To the contrary, it promotes both, understanding, interpretation and innovation of research, and the practical application. These facilitations of promotion are accompanied by ease of falsification and faked data. Business models of open access publication open doors of temptations to undercut science by anticipated profit. Previously serious publishers are already spoiled, and the scientific community should be aware that global investors are already misusing modern communication in science and research for their profit interest

History and structures of telecommunication in pathology, focusing on open access platforms

<p>Abstract</p> <p>Background</p> <p>Telecommunication has matured to a broadly applied tool in diagnostic pathology.</p> <p>Technology and Systems</p> <p>Contemporary with the development of fast electronic communication lines (Integrated digital network services (ISDN), broad band connections, and fibre optics, as well as the digital imaging technology (digital camera), telecommunication in tissue - based diagnosis (telepathology) has matured. Open access (internet) and server - based communication have induced the development of specific medical information platforms, such as iPATH, UICC-TPCC (telepathology consultation centre of the Union International against Cancer), or the Armed Forces Institute of Pathology (AFIP) teleconsultation system. They have been closed, and are subject to be replaced by specific open access forums (Medical Electronic Expert Communication System (MECES) with embedded virtual slide (VS) technology). MECES uses php language, data base driven mySqL architecture, X/L-AMPP infrastructure, and browser friendly W3C conform standards.</p> <p>Experiences</p> <p>The server - based medical communication systems (AFIP, iPATH, UICC-TPCC) have been reported to be a useful and easy to handle tool for expert consultation. Correct sampling and evaluation of transmitted still images by experts reported revealed no or only minor differences to the original images and good practice of the involved experts. β tests with the new generation medical expert consultation systems (MECES) revealed superior results in terms of performance, still image viewing, and system handling, especially as this is closely related to the use of so - called social forums (facebook, youtube, etc.).</p> <p>Benefits and Expectations</p> <p>In addition to the acknowledged advantages of the former established systems (assistance of pathologists working in developing countries, diagnosis confirmation, international information exchange, etc.), the new generation offers additional benefits such as acoustic information transfer, assistance in image screening, VS technology, and teaching in diagnostic sampling, judgement, and verification.</p

Extralobular Sequestration

Lung sequestration is a radiological/clinical diagnosis displaying with a mass of lung parenchyma that is not connected to the tracheobronchial tree. Intralobular sequestration defines lung parenchyma that is covered by visceral pleura; extralobular sequestration defines lung parenchyma that lies outside the visceral pleura. We report the histological findings of a 71 years old women suffering from chronic cough, recurrent bronchopneumonias, and several radiological densities in the left lower lobe (lingula). A resection of the lingula was performed. The histological findings include focal active fibrosis and marked media hyperplasia and dislocalization of pulmonary arteries as well as a tumorlet of carcinoid type and focal adenomatous hyperplasia (AAH). Differential diagnosis: Pulmonary Hypertension, Venous occlusive disease, Congenital malformatio

Open Access Publication In Pathology – Advantages, Constraints And New Tools

Introduction/ Background Open access journals are financed by authors (i.e. re- search grants), rather than by readers or subscribers. This business model allows a world – wide uncontrolled distribution of medical information and scientific knowledge. The financial of shifting the finance and the opportunities for misuse raise significant concerns regarding non – scientific impact and article content integrity. Aims Herein we report and discuss ideas and experiences of open access publication focusing on diagnostic pathology. Methods Our experiences are drawn from the open access online journal diagnosticpathology.eu. The journal offers the opportunity to publish case reports “beside the microscope” and to submit data for “interactive publication”. Both tools are unique, and cannot be found elsewhere. For publication of suitable articles, we demand the submission of glass slides, which will become completely digitized (virtual slides, VS). Results The journal is online since ten months, and the only completely independent open access journal in medicine. We have published several case reports under the headline “How do I diagnose…?” The presented form offers a guide through the article and permits a complete publication “besides the microscope”, commonly in less than one hour. Automated links to reference search items are included as well as virtual slides. The strict publication format permits fast submission of unique or interesting cases, and, in addition, the implementation of the publication into a case – related open and flexible image date bank.  Conclusions The mandatory inclusion of virtual slides is a unique quality control. The journal diagnosticpathology. eu is embedded in a cloud that will consist of an archive of published cases with virtual slides, an express review forum with a corresponding duty plan, an automated measurement system of histological slides, and open access atlases such as hazards of natural and artificial fibers (fine granulate)  and a  collection of  all known pulmonary diseases. Acknowledgement The financial support of the Verein zur Förderung des biologisch - technologischen Fortschritts in der Medizn e. V. is gratefully acknowledged.

Whole body plastination, intra-organ heterogeneity, and tissue based diagnosis – a survey

 Background: The corpse is the final structural relict of life. Its detailed analysis, the autopsy formed the basis and contributed significantly to our understanding of location, function and interaction of organs in man. Today, autopsies are performed rarely. They have been replaced by radiological in vivo visualization techniques and the analysis of organ excisions and biopsies. Which attributes do whole body preservations possess in this context? Techniques of Whole Body Analysis: In vivo imaging transfers the appearance of body organs and cellular structures in virtual images. The patient’s exposure to X-rays, fundamental particles (electrons, positrons, etc.), strong magnetic fields (nuclear resonance), or ultra sounds release the corresponding signals. The obtained images are interpreted in search for local abnormalities such as cancer, acute and chronic infections, inborn errors, hypertrophy or atrophy. Autopsies require the removal and visual inspection of organs shortly after the victim’s death. In addition, tissue probes of suspicious lesions are fixed and microscopically analyzed. The search for gene or protein abnormalities are added dependent upon the clinical history and gross findings. The whole body plastination is performed in separated steps which include fixation, anatomical dissection, forced polymer impregnation, positioning and curing. Organs and other tissue structures can be taken out of the body and separately demonstrated, or aligned and fixed within the body. Additional tissue examinations are possible at this stage, which is followed by hardening and fixation of the still flexible body. Fixation is done with heat, light or gas.   Results and Interpretation: Tissue conservation is a prerequisite to analyze and investigate in diagnosis and forecast of disease occurrence and behaviour. In history, autopsies have opened the door to localize the position and to understand the functions of organs. Today, they have been replaced by tissue banking and in vivo examinations in a wide range, especially when local lesions of organs are under investigation. Analysis of blood and serum is the main technique to search for organ dysfunction. Whole body plastination is an appropriate technique to investigate and demonstrate healthy appearance of organs, intra-organ heterogeneity, connection to and communication with neighbouring or distant organs as well as localization and distribution of organ lesions, and the associated functional impact. Perspectives: Modern societies try to inform their citizens by numerous investigations of the public health status and to improve the health condition as well as to minimize the development of behaviour associated diseases such as smoking and lung cancer, or overweight and infarction. Well performed body conservation supports these efforts. In addition, it can be considered an innovative technique to understand, diagnose, and even treat dysfunction of intra-body communication at the physical and even mental level.    

Cognitive Algorithms and digitized Tissue – based Diagnosis

Aims: To analyze the nature and impact of cognitive algorithms and programming on digitized tissue – based diagnosis. Definitions: Digitized tissue – based diagnosis includes all computerized tissue investigations that contribute to the most appropriate description and forecast of the actual patient’s disease [1]. Cognitive algorithms are programs that encompass machine learning, reasoning, and human – computer interaction [2]. Theoretical considerations: Digitized blood data, objective clinical findings, microscopic, gross, radiological images and gene alterations are analyzed by specialized image analysis methods, and transferred in numbers and vectors. These are analyzed by statistical procedures. They include higher order statistics such as multivariate analysis, neural networks and ‘black box’ strategies, for example ‘deep learning’ or ‘Watson’ approaches. These algorithms can be applied at different cognitive ‘levels’, to reach a digital decision for different procedures which should assist the patient’s health condition. These levels can be grouped in self learning, self promoting, self targeting, and self exploring algorithms. Each of them requires a memory and neighbourhood condition. Self targeting and exploring algorithms are circumscribed mechanisms with singularities and repair procedures. They develop self recognition.   Consecutives: Medical doctors including pathologists are commonly not trained to understand the basic principles and workflow of applied or potential future procedures. At present, basic medical data only serve for simple cognitive algorithms. Most of the investigations focus on ‘deep learning’ procedures. The applied learning and decision algorithms might be modified and themselves be used for ‘next order cognitive algorithms’. Such systems will develop their own strategies, and become independent from potential human interactions. The basic strategy of such IT systems is described herein. Perspectives: Medical doctors including pathologists should be aware about the abilities to enhance their work by supporting tools. In some case the users may not be able to fully understand these tools. Furthermore, these tools will probably become self learning, and, therefore, seem to propose the daily workflow probably without any medical control or even interaction

Cytology consultations with associated image quality evaluation – experiences of the Virtual International Pathology Institute (VIPI)

Background: The virtual international Pathology Institute (VIPI, www.diagnomx.eu/vipi) is the only image consultation forum that is organized in close organization to a conventional institute of pathology. Its approximately 160 experts in pathology and cytology consult and diagnose difficult cases on the basis of a convent weekly duty plan.  Herein we report the consultation results of a specific series of cytology specimens, and discuss potential application in routine virtual cytology. Material and Methods: Still images of fine needle aspirations sent for consultation to VIPI were evaluated by five members of VIPI. A total of forty and seven cases was analyzed, and scored in four classes (benign, probably benign, probably malignant, and malignant). In addition, the consultants evaluated and graded their impression of colour, focus and general image quality in 10 classes (10 = very good 1 = not acceptable). Automated measurements of objective image quality, calculation of the regions of interest (ROI), and automated diagnosis classifications were performed too. Results: The experts’ diagnostic conformity was computed 4.2/5; i.e., at average 4.2 experts stated the same diagnosis of each case. The automated classification supported the summarized experts’ diagnoses in 38/47 cases. The experts interpreted the image quality diversely. Two of them evaluated with tendency of low, and two of them of high grades. The individual interactive image quality evaluations showed statistically significant relationship to the diagnostic accuracy (p<0.05). A helpful and correct automated ROI detection was stated in more than 95% of images. Conclusion: The study indicates that electronic transmission of acquired conventional cytology smears is a useful tool to get access to experts’ knowledge worldwide. The case related diagnostic agreement of experts can serve for gold standard of virtual cytology (for example conformity > 80%). Additional automated measurements might support the diagnosis. Implementation of virtual slide technology and automated ROI visualization are additional tools in order to support the diagnostic accuracy. Virtual international pathology institutions are able to successfully work together with or even replace conventional cytology laboratories