**3. Whole slide imaging/virtual microscopy**

The introduction of whole slide imaging (WSI) has created some wonderful opportunities for the pathologist or generally speaking for the morphologist or biologist. It allowed capturing images of the entire pathology slide without the need to select only a few regions of interest. The new platforms with 64 bit and quad-core processors and the development of high-resolution cameras allowed the manufacturing of digital slides at high resolution harboring uniquely multiple magnifications and focal planes. This set of data processed in a computer allows a full simulation of light microscopy. The operator (e.g., pathologist or technologist) can scan the slides rapidly and focus zooming in and out in the monitor using the keyboard, mouse, or his/her finger determining the quality of the image and gathering information to make the diagnosis. The robotic microscopic scanner mechanically scans histologic glass slides containing the tissue already processed and stained. A software combines individual scanned fields into a composite digital image [11–14]. The acquisition time has been reduced since a scanner was commercialized and time, which has been a limiting factor, will shorten even further in the future. The operator may be able to open the final file using several viewing software with optional user-friendly interfaces. This procedure makes it possible for the operator to navigate to various areas of the virtual slide or zoom in/out changing the magnifications without operating a revolver. The new technology applied with the WSI can be used for primary diagnosis by the pathologist, for publication of scientific data in peer-reviewed biomedical journals, to capture static images for reporting, archiving or computer-aided analysis, and educational activities in the setting of new concepts for universities and hospitals. A few decades ago the introduction of multi-headed microscopy allowed multiple viewers to follow the operator navigating a light microscope connected with few guest binoculars. This simple step was multiplied using a camera connecting the microscope with a big screen able to open the participation of guests from dozens to hundreds. However, the virtual microscopy has opened the scenario to unrestricted access to viewing, no need to recut slides for teaching and overcome the quality deterioration of staining. The WSI slides are obviously more interactive than static images. They are easier to share with multiple users on several platforms, they can work on diverse operating systems, anywhere and at any time. Training materials can be standardized. Moreover, files can be made available by hyperlinks using restricted codes to access specific file servers [11–14]. Since the introduction of virtual microscopy, we have faced numerous and virtually unlimited educational activities, including graduate schools, training in different medical specialties, E-learning, and tele-education for remote communities that are not easily accessible. Education has not been limited to medical only but involved dental, biological, and veterinary schools worldwide [15]. There are e-learning and virtual workshops with virtual atlases on the web that have been able to be a primary source for hundreds or thousands of new doctors. The virtual microscopy has started a revolution promoting knowledge, which is web-based learning and made available by several societies including the United States and Canadian Academy of Pathology (USCAP), the International Academy of Pathology, and the International Academy of Cytopathology (IAC) [16]. In the United Kingdom (UK), the National Health Service (NHS) promotes Clinical Governance and clinical excellence with a specific institute

**159**

*Digital Pathology: The Time Is Now to Bridge the Gap between Medicine and Technological…*

nationwide labeled National Institute for Health and Care Excellence (NICE) [17]. Clinical governance describes a systematic approach to maintain and improve the quality of patient care. In similarity to the plan-do-check-act cycle, which is also known as Deming or Shewhart cycle, the clinical governance constitutes an official and unique framework through which the NHS is accountable for the ongoing improvement of quality of the clinical service with the aim safeguarding high standards of clinical care and creating a crucial environment focused on clinical excellence. Although communication failure is the most likely cause for medical errors, a substantial number of errors may be linked to a decrease of professional skills contributing to fatalities in healthcare. In 1999, Quality System Essentials were promoted to laboratory practices by the National Committee specifically for Clinical Laboratory Standards (now Clinical Laboratory Standards Institute [CLSI]). The essentials identify 10 or more major laboratory activities that are important components of a laboratory quality program [2, 3]. The updated and modernized quality system essentials that should be provided to each operator (e.g., pathologist) include updated equipment, smooth improvement of the diagnostic process, regular assessment and measurement of safety, and professional and personal development among others. All of these essentials were established to guarantee that data reported from the diagnostic laboratory unit are as accurate as possible. They should serve the requirements of both patients and clinicians. An imperative component in the control of any laboratory procedure is the constant and diligent participation of the operator in an external quality assurance (EQA) or proficiency testing program to validate that the operator is updated with the diagnostic criteria and skills are maintained. An EQA plan in place allows the healthcare to provide (University or hospital) to be certain that quality indicators are in place. There are numerous EQA programs worldwide, and they constitute a fundamental part of continuing professional development (CPD) of health care professionals [4]. The purpose of EQA in pathology is both to maintain good running standard operating procedures and to improve the performance of all sub-specialties. It will ensure that patients have access to a high-quality service wherever they live without constraints of physical barriers. Previously, we compared four slide survey programs from four geographical regions (United Kingdom, Germany, USA-Canada, and Australasia) concerning the EQA in pathology for pediatric pathologists in the setting of continuing professional development [17]. We found that the United Kingdom scheme, which has specific time frames (2 circulations/year, 30 slides), partial confidentiality, and numerous sources of data and assessors, can be used as an archetypal for revalidation. The US-Canadian and Australasian schemes only partially seem to fulfill the revalidation requirements. The German IAP scheme appears to be essentially an educational program and may be unsuitable for revalidation. WSI is widely implemented in the Australasian QA programs of the Royal College of Australia. The diagnostic scores of the pathologists undergoing the College promoted Performance Improvement Program (PIP) in Surgical Pathology online only without using histological glass slides do not appear compromised by the converting to WSI [18]. Pathology is in the center of a radical transformation in medicine, which is driven by many factors. Foremost, there is the advancement of precision medicine, an imbalance of pathology jobs across regions, and a need for more efficiency and effectiveness in the diagnostic workflow. In healthcare, technological innovation and its implementation at several sites are growing at an increasingly fast pace across specialties. Pathologists spend 30–40% of their work with administrative duties, and the frustration may exasperate with an increasing rate of burnout colleagues in several countries. The number of duties may be simplified, and technological innovation may help the pathologist to decrease the burden of the diagnostic procedures, but also install a system to red flags situations that may be borderlines. The introduction of AI in WSI will be the next step and will

*DOI: http://dx.doi.org/10.5772/intechopen.84329*

#### *Digital Pathology: The Time Is Now to Bridge the Gap between Medicine and Technological… DOI: http://dx.doi.org/10.5772/intechopen.84329*

nationwide labeled National Institute for Health and Care Excellence (NICE) [17]. Clinical governance describes a systematic approach to maintain and improve the quality of patient care. In similarity to the plan-do-check-act cycle, which is also known as Deming or Shewhart cycle, the clinical governance constitutes an official and unique framework through which the NHS is accountable for the ongoing improvement of quality of the clinical service with the aim safeguarding high standards of clinical care and creating a crucial environment focused on clinical excellence. Although communication failure is the most likely cause for medical errors, a substantial number of errors may be linked to a decrease of professional skills contributing to fatalities in healthcare. In 1999, Quality System Essentials were promoted to laboratory practices by the National Committee specifically for Clinical Laboratory Standards (now Clinical Laboratory Standards Institute [CLSI]). The essentials identify 10 or more major laboratory activities that are important components of a laboratory quality program [2, 3]. The updated and modernized quality system essentials that should be provided to each operator (e.g., pathologist) include updated equipment, smooth improvement of the diagnostic process, regular assessment and measurement of safety, and professional and personal development among others. All of these essentials were established to guarantee that data reported from the diagnostic laboratory unit are as accurate as possible. They should serve the requirements of both patients and clinicians. An imperative component in the control of any laboratory procedure is the constant and diligent participation of the operator in an external quality assurance (EQA) or proficiency testing program to validate that the operator is updated with the diagnostic criteria and skills are maintained. An EQA plan in place allows the healthcare to provide (University or hospital) to be certain that quality indicators are in place. There are numerous EQA programs worldwide, and they constitute a fundamental part of continuing professional development (CPD) of health care professionals [4]. The purpose of EQA in pathology is both to maintain good running standard operating procedures and to improve the performance of all sub-specialties. It will ensure that patients have access to a high-quality service wherever they live without constraints of physical barriers. Previously, we compared four slide survey programs from four geographical regions (United Kingdom, Germany, USA-Canada, and Australasia) concerning the EQA in pathology for pediatric pathologists in the setting of continuing professional development [17]. We found that the United Kingdom scheme, which has specific time frames (2 circulations/year, 30 slides), partial confidentiality, and numerous sources of data and assessors, can be used as an archetypal for revalidation. The US-Canadian and Australasian schemes only partially seem to fulfill the revalidation requirements. The German IAP scheme appears to be essentially an educational program and may be unsuitable for revalidation. WSI is widely implemented in the Australasian QA programs of the Royal College of Australia. The diagnostic scores of the pathologists undergoing the College promoted Performance Improvement Program (PIP) in Surgical Pathology online only without using histological glass slides do not appear compromised by the converting to WSI [18]. Pathology is in the center of a radical transformation in medicine, which is driven by many factors. Foremost, there is the advancement of precision medicine, an imbalance of pathology jobs across regions, and a need for more efficiency and effectiveness in the diagnostic workflow. In healthcare, technological innovation and its implementation at several sites are growing at an increasingly fast pace across specialties. Pathologists spend 30–40% of their work with administrative duties, and the frustration may exasperate with an increasing rate of burnout colleagues in several countries. The number of duties may be simplified, and technological innovation may help the pathologist to decrease the burden of the diagnostic procedures, but also install a system to red flags situations that may be borderlines. The introduction of AI in WSI will be the next step and will

*Interactive Multimedia - Multimedia Production and Digital Storytelling*

**3. Whole slide imaging/virtual microscopy**

Picture Archiving and Communication System (PACS), which will permit an efficient way of seeking pathology images. This aspect will be possible, thanks to the Digital Imaging and Communications in Medicine (DICOM) image format, which is being used for radiology images and adapted to be also used for pathology images.

The introduction of whole slide imaging (WSI) has created some wonderful opportunities for the pathologist or generally speaking for the morphologist or biologist. It allowed capturing images of the entire pathology slide without the need to select only a few regions of interest. The new platforms with 64 bit and quad-core processors and the development of high-resolution cameras allowed the manufacturing of digital slides at high resolution harboring uniquely multiple magnifications and focal planes. This set of data processed in a computer allows a full simulation of light microscopy. The operator (e.g., pathologist or technologist) can scan the slides rapidly and focus zooming in and out in the monitor using the keyboard, mouse, or his/her finger determining the quality of the image and gathering information to make the diagnosis. The robotic microscopic scanner mechanically scans histologic glass slides containing the tissue already processed and stained. A software combines individual scanned fields into a composite digital image [11–14]. The acquisition time has been reduced since a scanner was commercialized and time, which has been a limiting factor, will shorten even further in the future. The operator may be able to open the final file using several viewing software with optional user-friendly interfaces. This procedure makes it possible for the operator to navigate to various areas of the virtual slide or zoom in/out changing the magnifications without operating a revolver. The new technology applied with the WSI can be used for primary diagnosis by the pathologist, for publication of scientific data in peer-reviewed biomedical journals, to capture static images for reporting, archiving or computer-aided analysis, and educational activities in the setting of new concepts for universities and hospitals. A few decades ago the introduction of multi-headed microscopy allowed multiple viewers to follow the operator navigating a light microscope connected with few guest binoculars. This simple step was multiplied using a camera connecting the microscope with a big screen able to open the participation of guests from dozens to hundreds. However, the virtual microscopy has opened the scenario to unrestricted access to viewing, no need to recut slides for teaching and overcome the quality deterioration of staining. The WSI slides are obviously more interactive than static images. They are easier to share with multiple users on several platforms, they can work on diverse operating systems, anywhere and at any time. Training materials can be standardized. Moreover, files can be made available by hyperlinks using restricted codes to access specific file servers [11–14]. Since the introduction of virtual microscopy, we have faced numerous and virtually unlimited educational activities, including graduate schools, training in different medical specialties, E-learning, and tele-education for remote communities that are not easily accessible. Education has not been limited to medical only but involved dental, biological, and veterinary schools worldwide [15]. There are e-learning and virtual workshops with virtual atlases on the web that have been able to be a primary source for hundreds or thousands of new doctors. The virtual microscopy has started a revolution promoting knowledge, which is web-based learning and made available by several societies including the United States and Canadian Academy of Pathology (USCAP), the

International Academy of Pathology, and the International Academy of

Cytopathology (IAC) [16]. In the United Kingdom (UK), the National Health Service (NHS) promotes Clinical Governance and clinical excellence with a specific institute

**158**

help to increase the accuracy of pathology diagnosis and reporting. The introduction of algorithms that allow the machine to follow the diagnostic procedure operated by the pathologist using an eye tracking system and algorithms able to identify the discrepancies of pathology reports before signing out will help in the aim to reach extreme accuracy in medicine. The breakdown of geographical barriers operated by WSI will be implemented by the next step of a new healthcare system where AI will support the diagnostic procedure. There will be an enhanced collaboration allowing pathologists to seek second opinions more quickly, collaborating with multidisciplinary care teams more effectively, and distribute workloads across sites more evenly. Data from patient's history and unique risk factors will be studied by a background algorithm allowing the pathologist to have a companion for suggested differential diagnoses. The integration of data across clinical systems, lab examinations, and radiology with pathology images applying artificial intelligence to derive understandings is called computational pathology, which is far more convoluted than a file with stacked images of a glass slide. This revolution will implement the highest levels of accuracy and can be implemented to any specialty. This scenario is happening now as evidenced by the most recent congress of European urologists. Prof. Guo from Nanjing, China, claimed that smart software could diagnose prostate cancer as well as a pathologist (https://eau18.uroweb.org/smart-software-can-diagnose-prostatecancer-as-well-as-a-pathologist/). All these algorithms seem to reconnect to the Bayes' theorem, which benefits us finding the probability of an event A given event B, written P(A|B), in terms of the probability of B given A, written P(B|A), and the single probabilities of A and B. Consequently, P(A|B) = P(A) \* P(B|A)/P(B). Thus, in this scenario, event A is the event the patient has a specific disease, and event B is the event that the patient's test is positive. Thus, P(B|notA) represents the probability of a "false positive" rate, i.e., the patient's test is positive even though the patient does not have the disease. If the specific disease has an incidence of one in 10,000 people and a specific test has an accuracy of 99%, P(B|A) = 0.99, P(A) = 0.0001, and P(B) may be consequent by conditioning on whether event A does or does not occur, i.e., P(B) = P(B|A) \* P(A) + P(B|notA) \* P(notA) or 0.99 \* 0.0001 + 0.01 \* 0.9999. Thus, the ratio the pathologist gets from Bayes' theorem is less than 1%. This result relies on the disease, which is very rare. The number of false positives significantly surpasses the people who truly have the disease.
