Advantages of digital pathology

With the advent of the ever evolving powerful and sophisticated computing and data storage technologies including hardware and software, pathology is embracing the digitization technologies at a rapid pace. Pathologists are using dig ital imaging for simple tasks like image archiving to the more complex activities like telepathology, image analysis etc.¹

Simple image acquisition has now advanced to whole slide imaging (WSI), a novel technology also referred to as “virtual microscopy”. WSI involves digitization of complete slide generating images of the slide just as we see in the light microscope, by using specialized scanner (hardware) in the form of large representative digital image (also called “digital slide”). The enormous digital image files so generated are viewed using specialized software also called “virtual slide viewer”. Thus, digital pathology solutions provide high resolution slide scanning, virtual storage of digital slides and analysis and interpretation of histological images on computer screen or smart phones.

Illustration taken from internet, courtesy: Russ Granzow. http://www.philips.com/aw/innovationmatters/blog/examining-digital-pathologys-increasingly-important-rolein-care.html²⁰ for the purpose of dissemination and enhancement of knowledge.

Employment of WSI for educational research and academic activities including graduate and professional education, virtual tutoring and performance improvement programmes offer many advantages over traditional glass slides², ³-⁴. Digital slides can be made available to multiple remote users, easily annotated, are more interactive, and useful for promoting quality standardization of training materials as same slide sets are available for all trainees. Using WSI platforms, highest quality slides of the most representative sections can be easily archived for educational purpose without risk of fading, breaking and losing. Digital slides facilitate use of rare or exotic specimens, cytological slides and small biopsies with scant material where multiple sections are not possible, in teaching aids, which otherwise are not incorporated in teaching due to scarcity.

The clinical usage of WSI ranges from telepathology for primary diagnosis to second opinions, remotely interpretations of frozen sections, and viewing immunostain for showing slides at tumour boards. A number of publications have shown good diagnostic concordance between WSI and glass slides⁵,⁶,⁷-⁸.

Exploits of high speed internet and cloud solutions with WSI are facilitating global digital pathology network allowing users around the world to connect on the clinical front, which has compelled leading researchers and venders to join hands for improving WSI platforms including high definition Hematoxylin and Eosin staining for digital pathology⁹, colour calibration slide for colour standardization in WSI¹⁰, and vender neutral viewing software (e.g., OpenSlide)¹¹. Software have been developed that can stitch together smaller individual images to generate a pseudo whole mount section (e.g., Histostitcher)¹², or align whole slide images of serial sections which allow users to perform virtual double staining to co-localize biomarkers, and generate and manipulate 3D structures to better reconstruct and visualize tissue morphology, assess positional relationships between area of interest and surrounding structures, and obtain new measurements¹³. A novel Fourier pytchographic microscopy method has been developed recently which rapidly stitch together thousands of low resolution images to provide a wide-field, high resolution images, thus reducing drastically the time needed to scan a whole slide¹⁴. Future enhancements of features such as multilevel scanning of whole slides to replicate z-axis focus function of a microscope and extended focus imaging enabling to merge multilevel images together will allow whole section in focus at every point. With the development of such features, the slide scanner may provide a new perspective that cannot be achieved on a microscope¹⁵.

Many pathology departments in the western countries have already developed and installed an automated inhouse interface by integrating their Lab Information System with WSI software and creating bioinformatics solutions that support integration of heterogeneous data sets including clinical, next generation sequencing and imaging data¹⁶.

Pathologists apart, the industry is also starting to shift from physical slide sample analysis to digital image analysis. Increasing global prevalence of chronic diseases, rising demand for faster and accurate pathology test results, automation of pathology systems and supportive government initiatives are driving the growth of the digital pathology market. Increasing cancer mortality is pushing the need for faster diagnosis mechanisms. According to the WHO, a cancer diagnosis is expected to increase by 70% in the next two decades with an estimated 1.41 million misdiagnoses of cancer globally¹⁷. Manufactures are striving to provide accurate and effective diagnosis solutions for cancer diagnosis. With over 30 companies worldwide providing digital pathology hardware, software and services, the global digital pathology market, valued at USD 248.4 million in 2013, is expected to grow at a compound annual growth rate of over 12% up to 2022¹⁸. North America dominates this market followed by Europe and Asia¹⁴. The Asian market is expected to have the highest growth over the next several years due to an increased awareness of the many potential benefits and the promotion of digital pathology by the Ministries of Health in Asia to improve the quality of cancer diagnosis. Successful programs such as NHS England′s National Pathology Programme′s, Digital First: Clinical Transformation through Pathology Innovation will help to drive adoption of this evolutionary technology¹⁹.

The benefits of digital pathology are clear which addresses the limitations of traditional pathology work flow. Some of the advantages and challenges of digital pathology are enlisted below.

Advantages of digital pathology

With digitization, pathology lab can increase organization, streamline processes, increase caseloads, and reduce turnaround time, thus obviating many day to day logistic oriented delays in traditional lab.

Pathology digitization facilitates remote communication and collaboration across locations and specialties.

Cross functional integration and aggregated views of a patient clinical data help better informed decision making.

As larger sets of clinical data can be archived and tracked by digitization, access to a larger volume of expert knowledge can lead to advancement in diagnostics and uncover of new insights.

Digital pathology enables instant sharing of results with multiple departments and colleagues, inclusion of digital images with pathology report, computerized quantitative analysis for prognosis scores, eliminating risk of break of glass slides in transit and so on.

Digital pathology enables performing automatic case reviews and tracking of slide assessment for completeness, in addition to image analysis efficiency, precision and reproducibility, thus substantially improves quality assurance.

As a teaching aid, digital slides with inherent robustness and longevity are a great advancement over glass slides which may fade, break or loss. Digital scan of a single tissue specimen can provide slides for several teaching classes and enables students to experience a wider range of cases.

Besides facilitating image sharing and collaboration for a variety of cases, enabling efficiencies in tumour boards, second opinions and access to subspecialty expertise, automated digital imaging analysis in clinical setting such as diagnostic HER2 assay, enables reproducible and objective stratification of patients into cohorts of likely responses to drug therapies and eliminate inter- and intra-observer interpretation variability.

With increased sub specialization of pathologists, the ability to engage with experts in a given field is greatly enhanced by digital pathology, which helps with difficult evaluations and streamlines access to the right experts, with ultimate improvement in turnaround time for decision support to the benefit of researcher, healthcare provider and patient.

Digital pathology will enable pathologists and pathology departments to be more efficient. The ability to view images from any location in the world will allow them to be more flexible and to provide specialist or second opinion quickly, thus providing responses rapidly and accurately, especially with routine cases, which will give more time for dealing with difficult cases.

As digital pathology enables collaboration between pathologists as well as within cross-disciplinary teams, pathology labs will be able to offer expertise to regions beyond their current scope where experienced or specialized pathologists are scarce.

The digital pathology will provide lead to greater efficiencies in lab work flow, provide decision support tools and transform the interaction between oncologists, pathologists and patients, as well as researchers, instructors and students.

Challenges of digital pathology

Generally pathologists tend to be traditionalists, and combined with lack of regulatory approvals in many parts of the world, they are cautious of treading into new area. While digital pathology makes collaborating faster, compared with shipping slides or getting a pathologist to travel to different locations, the user experience when viewing digital slides could be slower than that of a microscope, if users lack familiarity with the system, or if they need training or face limited networking.

Another important factor is pathologists are short of time. Increased workloads of routine diagnosis and disease investigation, and more so of identifying new markers required for diagnosis, pathologists are facing scarcity of time to commit to new training and to consider testing a digital solution compared with their current methods.

Pathologists will still need convincing of the benefits of sharing images and the fact that the time needed to view a case from a digital image can be as fast as viewing using a microscope.

Concerns about integration of digital pathology with existing work flow, IT infrastructure, connectivity and scalability could be a major hindrance. In less developed world, networking infrastructure including internet speed and bandwidth for transferring large image files could be an issue for execution of digital pathology, although with faster computers and better networking technologies, the gap is closing.

The cost of system acquisition combined with concerns of return on investment could be a factor inhibiting the implementation, and the total cost of ownership can be higher than expected too.

There is no clear guidance from regulatory authorities about validity of using digital slides to report cases. Pathologists may be concerned about their legal position in case of misdiagnosis using a digital slide displayed on a computer screen. Also, there are no guidelines on reporting from a digital image and need of standard process to integrate the work flow. Regulators and slide scanning companies need to sit together to optimize the process so that pathologists can benefit fully from this new technology.

Digital pathology workflow is quite different. The very high resolution, highly detailed images result in massive files, may be in gigabytes rather than megabytes, so storage will be real challenge. Further, most files are in proprietary formats which cannot be opened using standard software. The way of making files viewable to others is important, especially when another pathologist will see the slides using different monitors.

Quality assurance of the image could be a basic issue. The scale of an image on computer monitor is different from the same image viewed through microscope, and optical resolution is different from digital resolution, so right setup of equipment will be a priority.

Potential conflict may arise between patents and standards when implementation of standard necessitates use of technology protected by patents.

Different venders use proprietary imaging technologies, which may create problems with compatibility both backwards and forwards.

Russ Granzow, General Manager of Philips Digital Pathology Solutions, summarizes the importance of digital pathology in healthcare in the best possible way: “While nothing can replace the knowledge of the pathologist, unlocking and augmenting their knowledge through digitization will have a great impact on future of health care. As digital pathology becomes more sophisticated, more information about a specific tissue sample can be collected, catalogued and shared for a better understanding of a specific disease or patient population. As pathology continues its evolution and becomes more connected across the healthcare continuum, health systems and their multidisciplinary teams will also benefit from pathology′s increasingly important role in care, which has the potential to lead to better health management and more accurate, confident patient diagnoses”²⁰.

Ushering in the era of digital pathology…