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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 13  |  Issue : 4  |  Page : 283-288

Virtual microscopy: The future of pathological diagnostics, dental education, and telepathology


1 Department of Oral Pathology and Microbiology, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India
2 Department of Public Health Dentistry, Postgraduate Institute of Dental Sciences, Rohtak, Haryana, India
3 Department of Oral Pathology, NIMS Dental College, NIMS University, Jaipur, Rajasthan, India
4 Department of Oral Pathology, SR College of Dental Science, Faridabad, Haryana, India
5 Department of Oral Pathology, Government Dental College, Jaipur, Rajasthan, India

Date of Submission01-Nov-2020
Date of Acceptance04-Feb-2021
Date of Web Publication08-Oct-2021

Correspondence Address:
R M Vatchala Rani
Department of Oral Pathology and Microbiology, Faculty of Dentistry, Jamia Millia Islamia, Jamia Nagar, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJDS.IJDS_194_20

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  Abstract 


Objectives: The objectives of this study were as follows: (1) to provide an overview of the feasibility, utility, merits, and demerits of virtual microscopy (VM) in pathological diagnostics and (2) to evaluate its advantages in dental and medical teaching over conventional microscopes. Materials and Methods: A literature survey was carried out in August 2020 in electronic databases such as PubMed using keywords such as virtual microscopy and whole slide imaging. The searches revealed 956 articles out of which 36 were selected after reading the full-text articles. Results: The review of 36 articles revealed that VM or whole-slide imaging (WSI) allows access to entire scanned sections of tissue that can be viewed on a computer in exactly the same way as conventional glass slides with a microscope and can be explored at several magnifications. VM offers many advantages like ease of accessibility through the Internet anytime or in any place, and moreover, the virtual slide does not get damaged or fade away like glass slide. Since it increases learning and comprehension, virtual microscopes have been used extensively in dental and medical education. Conclusions: VM opens a new world in tissue-based diagnosis through digitization of slides. The experiences of telepathology applications have already proved that it is a promising technology which has been adopted by histopathologists and cytologists across the world and contributing immensely to telepathology consultation in underserved areas. It is a feasible, valid, and approved technology for pathological diagnosis.

Keywords: Digital pathology, virtual slide, whole-slide imaging


How to cite this article:
Vatchala Rani R M, Manjunath B C, Bajpai M, Sharma R, Gupta P, Bhargava A. Virtual microscopy: The future of pathological diagnostics, dental education, and telepathology. Indian J Dent Sci 2021;13:283-8

How to cite this URL:
Vatchala Rani R M, Manjunath B C, Bajpai M, Sharma R, Gupta P, Bhargava A. Virtual microscopy: The future of pathological diagnostics, dental education, and telepathology. Indian J Dent Sci [serial online] 2021 [cited 2021 Oct 19];13:283-8. Available from: http://www.ijds.in/text.asp?2021/13/4/283/327813




  Introduction Top


The use of modern technology has transformed the whole world into a global village where accessibility to everything is the way of life. Health care has grown leaps and bounds with the application of science and technology enabling the delivery of evidence-based treatment procedures. Despite this, health care is not accessible to everyone giving rise to various health inequities. To bridge this significant gap in modern times, the technology is helping health care delivery systems so that health care is accessible for everyone. This branch of medicine where consultation, diagnosis, and treatment are provided through the use of World Wide Web (www) from across a distance to deprived areas is called telemedicine.[1],[2]

Another sub-branch of telemedicine which is involved with scanning, digitizing the slide, transmitting through www which can be viewed by a pathologist sitting in a different part of the world is called “telepathology”.[3] The pioneer to popularize the concept of “telepathology” was Ronald S. Weinstein, a pathologist. During various validation studies of surgical pathology and cytopathology, he encountered inter-investigator variability. In an effort to solve the inter-investigator variability, he came up with an innovative technique using dynamic-robotic telepathology that would potentially decrease the misdiagnosis among pathologists who were examining the virtual slides (VSs) and making diagnosis. Thus, a new field of pathology gave rise which is called “telepathology.” Dr. Weinstein et al. were instrumental in developing the first sub-1-min whole-slide imaging (WSI) system, the DMetrix DX-40 scanner, in the early 2000s which paved way for the field of digital pathology.[4]

Digital pathology has given rise to another important area called “virtual microscopy (VM)” which is characterized by acquisition of digitized slide through whole-slide scanning and transmitting it through high-speed Internet for rapid diagnosis.[5] Due to recent technological advancements, it has become possible to produce digital scans of a whole slide at a range of magnifications that produce a “VS” for remote viewing, in which case the distant viewer can control all functions of the “virtual” microscope.[6] VM represents one such simulation-based technology that has the potential to enhance student learning and readiness to practice while revolutionizing the ability to clinically diagnose pathology collaboratively across the world. While understanding that a substantial amount of literature already exists on VM, much more research is still required to elucidate the full capabilities of this technology.[7]

In the past few years, VM has been accepted widely across a pathologist around the world because of rapid advancements in the field of technology of image digitalization and transmission through the www. There are numerous applications of VM which ranges from clinical research and histology teaching to obtaining a second opinion. Notwithstanding the drawbacks such as cost of the virtual microscopes, requirement of a high-speed Internet, and availability of a huge memory backup, the VM offers promise to bridge the gaps of accurate diagnosis and enhancing medical and dental teaching.[8]

This review explores the use of VM in medical education and pathological diagnosis with a unique focus on key requirements needed to take this technology to the next level in its use in medical and dental education along with clinical practice.

Aims and objectives

The aims of this study were as follows:

  1. To document the feasibility, utility, merits, and demerits of VM in pathological diagnostics
  2. To evaluate its advantages in dental teaching over conventional microscopes.



  Materials and Methods Top


Search strategy

A literature survey was carried out in various electronic databases in August 2020 to identify the articles required for this narrative review on VM. MeSH terms/keywords such as “Virtual microscopy,” “Whole slide imaging,” “Digital pathology,” “telediagnostics,” “virtual slide, and “telepathology” were used to search in the electronic databases such as PubMed database, Scopus, Embase, Cochrane Library, and ScienceDirect, and a manual search was also done using the cross-references and textbooks. Articles published in English language from 2000 to August 2020 which fulfilled the objectives of the study were included.

Article selection criteria

The articles required for the review were selected based on the inclusion and exclusion criteria. Quality assessment was also carried out to select the articles required for this review.

Inclusion principles

  1. Studies on characteristics and utility virtual microscopes in pathological diagnostics
  2. Studies on digital pathology
  3. Studies on WSI
  4. Clinical trials, randomized controlled studies, and investigative reports.


Exclusion principles

  1. Animal-based studies
  2. Narrative reviews on VM or WSI
  3. Studies which did not use virtual microscopes for diagnostics.



  Results Top


The searches revealed 956 articles, out of which 115 were selected after reading the titles and abstracts. Fifteen articles were added from hand searching to obtain a total of 85 articles. After reading the full-text articles and applying the inclusion and exclusion criteria, 36 articles were selected for the review which fulfilled the objectives of the study.

Digital pathology

In recent times, digital pathology has been viewed as the technology of the 21st century which enables accurate diagnosis and also enhances dental and medical teaching. Many telepathology systems were developed such as dynamic (real-time) robotic telepathology and static image (store-and-forward) telepathology. Another system which combines both the static and dynamic telepathology systems is “hybrid dynamic-robotic telepathology system” that has become increasingly popular among pathologists across the world.[9] This has paved way for development of sustainable telepathology system with incorporation of “WSI technology” or “VM.” With rapid progress in digital imaging and application in digital pathology systems, various virtual microscopes have found increased acceptance among researchers, pathologists, and histologists for making accurate diagnosis when compared to conventional microscopes. In recent times, WSI technology has been emerging as the preferred choice because of various advantages of dynamic-robotic telepathology systems it offers when compared to compound microscopes.[10],[11]

The WSI-enabled dynamic-robotic telepathology module has been able to provide answers for various issues pertaining to focusing of the image. Many microscope manufacturers have developed virtual microscopes which have incorporated high-throughput digital technology apparatus which has excellent inter-examiner reliability.[12] Efforts are being made to commercialize the system so that “VM” can become sustainable so that it is accepted by a large number of pathologists and histologists. It has also revolutionized the delivery of pathology diagnostic services to the areas which have deficient access to accurate diagnosis of various diseases and conditions.[13]

Virtual microscopy (whole-slide imaging system)

Many of the disadvantages of conventional microscopy have been overcome by the use of “VM” or “WSI” which is a method of transmission of microscopic images over computer networks through the Internet. In this advanced form of technology, an entire microscopic image is scanned at high resolution, and then, those digital slides are stored in server and transmitted across networks with the use of high-speed Internet. The viewer of the digitized slides can access the entire histological section and can pan, zoom, and focus to view individual cell organelle and hence can make an accurate diagnosis.[14],[15]

The use of virtual microscopes has transformed traditional diagnostic systems by overcoming the dependence on physical space, equipment, and specimens. Moreover, digital slides can have a high resolution and are resistant to being damaged or broken over time. These virtual microscopes explore specimen focus, illumination intensity, magnification, and translation operating essentially in a manner that is identical to real-life microscopes.[16]

Components of whole-slide imaging technology[17]

The process of obtaining a VS involves four crucial steps such as

  1. Whole-slide scanning (image acquisition)
  2. Storing the digitized slide in a high-capacity server
  3. Editing the digital slides for color, brightness, and resolution
  4. Display of digitized slides
  5. Transmitting the VSs through www
  6. Making the diagnosis with the help of inbuilt diagnostic software which can be used for zooming and focusing individual cells.


WSI has been extensively studied in recent times. It consists of series of components including the capture device or whole-slide scanner which converts into “digital slide,” along network and storage infrastructure which make up “virtual microscope interface system. Digital slide is created by an imaging robot that digitizes an entire slide, field by field, at high resolution. The whole slide is digitally scanned by robotic scanner without any loss of information of the sectioned specimen. The main disadvantage is that the huge amount of data is generated (1–10) GB per slide which requires enormous amount of space in the server as well as high-speed Internet for transmission of digitized slides. The digitally scanned whole slide becomes “VS” which is an interactive microscope emulator that presents a complete digitized tissue section through the Internet.[17],[18]

Virtual slide

Once the VS is created, it becomes an interactive microscope emulator that can be transmitted rapidly through the Internet. The VS simulates the conventional microscopes which can be zoomed and panned from a resolution × 16 to × 2000 which enables a histopathologist to view at any magnification effortlessly. This is possible through the robotic whole-slide scanning units which capture the image at sufficiently high resolution and color depths.[19],[20]

Since VS is characterized by a huge size and requires enormous storage space, hence the images are resized to JPEG formats. Depending on server capacity, slide scanning is carried out in small and high volume (up to 1000 slides in a batch).[21] After digitized slide becomes a VS, it can be transmitted to any part of the world with the help of high-speed Internet through which telepathological consultations are possible.[16]

Image resolution

Resolution of a VS is very important as it prevents loss of information and enables accurate diagnosis as it can be panned and zoomed up to ×2000. The digitized slide can be viewed with greater detail in a large monitor or a computer screen which enables accurate diagnosis. Recent technology provides real-time images, allowing VSs to be viewed continuously. The applications of virtual microscopes allow a laboratory technician to transfer VSs to a pathologist sitting in different parts of the world. Whole-slide image viewers are used in different sectors such as medical diagnosis, intraoperative diagnosis, medical education, teleconsultations, clinical research, and immunohistochemistry.[22]

Al-Janabi et al.[23] have validated the sensitivity and specificity between WSI and conventional microscopy, and the concordance ranged from 90% to 94%. Krishnamurthy et al.[24] have reported that there were almost similar agreements between WSI and optical microscopy, but diagnosis was better among pathologists using optical microscopy (90.5% with WSI vs. 92.1% with OM). The reliability was also similar (91.6% with WSI in comparison with 94.5% for OM), while few authors have concluded that the diagnostic accuracy was not inferior using WSI when compared to conventional microscopy.[25]

Whole-slide image formats

There are several whole-slide image formats, but there are no standard versions because various manufacturers of virtual microscopes have their own image types [Table 1].[26],[27]
Table 1: Whole Slide Image formats

Click here to view


Virtual slide analysis/viewer software

To view a digital image, navigate, zoom out, and doing annotations, software is required to be downloaded on the desktop or laptop. Without the software, it is difficult to view the VSs in an interactive manner. The software also come preinstalled or downloaded from the site of the manufacturers of virtual microscopes such as three-dimensional Histotech, Leica's Aperio image scope, Hamamatsu, Philips, and Nikon Coolscope II, and it is also essential to install a correct software based on the type of the digital image. Image analysis software provides complete control over algorithms which make navigation easy and effortless.[28]

There are many software available which can open any type of microscopic image. After installation, VS can be inspected and can be navigated to any type of microscopic imaging file format available. Whether it is a macroscopic observation, WSI data, or fluorescent snapshot observation, it can display it all in a single easy to browse environment. There are various software which are freely available to download such as QuPath, Cytomine, Orbit, ASAP, and ImageJ, which are famous open-source medical imaging viewers, with a custom plugin called SlideJ. OMERO is a digital pathology server designed to store, manage, whole-slide images and provide developers with API. Other notable software are JVSView, PMA. start (Pathomation), and caMicroscope, which are open-source web-based digital pathology image viewers with support of human/machine-generated annotations and markups.[29],[30] [Figure 1]
Figure 1: Aperio Image scope software[31]

Click here to view


Uses of virtual microscopy

  1. To capture of digital images and convert it to digital slides
  2. It can be used in conferences and the image can be projected to an external screen using a projector
  3. For teleconsultation and the operations can be remotely handled, diagnosis of a particular specimen can be exchanged between many pathologists and histologists
  4. Useful in medical and dental education
  5. In medical and dental research
  6. Image analysis [Figure 1]
  7. Archival and retrieval of VSs
  8. Laboratory information system
  9. Secondary diagnostic consultations and VS sharing
  10. Facilitates rapid, efficient communication between subspecialty pathologists and generalist pathologists and obtaining the second opinion on challenging cases
  11. Fine-tuning of diagnostic interpretation
  12. Have numerous advantages over conventional glass slides.[37],[38],[39] [Figure 2]
Figure 2: Commercial virtual microscopy systems

Click here to view


Limitations of virtual microscopy

  1. It is costly to set up a VM system
  2. It has utility as the primary diagnostic tool than light microscope is not established
  3. Not approved by the regulatory bodies
  4. Continuous automated scanning is necessary
  5. High-large storage capacity interfaces
  6. Scanning quality and its validation studies are lacking.[39]



  Discussion Top


The VM is the need of the hour amid pandemic of COVID-19 as it reduces the risk of transmission of SARS-CoV-2. VM can be used immensely for teleconsultations, along with dental and medical education. Even though there are limitations such as high cost, storage, and requirement of trained personnel, VM is one technology that has revolutionized the learning of histopathology worldwide. Availability of high-speed Internet throughout the world has enabled pathologists to adopt VM in their daily practice. Even though it is not approved by many regulatory authorities, teleconsultations using VM have been vital to address access inequities in many deprived areas as VS can be conveniently visualized using specialized VM software on a computer or tablet device which makes it easy for teleconsultations.[20],[40]

The disadvantages of glass slides or photographs are ratified by the use of VS which allows pathologists to focus a particular area for better understanding of the cells and helps in performing a detailed study, thereby enabling an accurate diagnosis.[37],[38] VM has been used extensively in medical education and dental education, particularly training students in histology and pathology.[39],[41] Many studies have provided evidence that VM increases comprehension and also improves the diagnostic competencies among students as many VM software reproduce a high-quality image with meticulous clarity which enables students to visualize, pan, and zoom (up to a maximum of ×100).[19] [Figure 1]

The use of VM has a potential to transform the practice of pathology as real-time images can also be sent through the Internet to remote locations, including classrooms, laboratories, and dental and medical schools enhancing learning and comprehension among students as well as enabling histopathologists to make an accurate diagnosis. VM enables pathologists to share slides and discuss observations across various platforms and is boon during COVID times.[42],[43] More efforts are essential to increase the utilization and funding to establish digital pathology setups in institutions as well as in research laboratories. VM has a great scope in coming times considering the magnitude of COVID-19 pandemic.


  Conclusions Top


VM can revolutionize the practice of pathology in coming times. In the foreseeable future, VM can potentially replace glass slides and light microscopes in dental and medical education. VM with a completely digitized glass slide opens a new world in tissue-based diagnosis and has already proved that it is a promising technology.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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