APW-EDM White Paper

Foreword

This is the collaborative space of the white paper "Anatomic Pathology Workflow in an Era of Digital Medicine (APW-EDM)"

The latest draft of the white paper is downloadable from this folder

Temporary documents from Nicholas Jones available via dropbox

Current contributors are:

• Raj C. Dash, MD,
• Riki Merrick,
• Francesca Frexia,
• Francesca Vanzo, ,
• John D Nolan,
• Dan Rutz,
• Nicholas C. Jones,
• Gunter Haroske,
• François Macary,
• Larent Duval

Introduction

This document, the IHE PaLM “Anatomic Pathology Workflow in an Era of Digital Imaging” White Paper, describes use cases, data elements, actors, and transactions necessary to support anatomic pathology workflows that leverage digital technologies. Abbreviation for the title is APW-EDM.

This white paper lays out a collection of future integration profiles to address how vended systems for supporting anatomic pathology workflows interact and is intended to replace the former Anatomic Pathology Workflow (APW) profile. The first objective is to better take into account the latest advancements in digital imaging, spanning but not necessarily limited to two primary aspects of anatomic pathology workflow:

• the gross/macroscopic examination leveraging state-of-the art more interoperable imaging modalities,
• the histologic/microscopic examination taking advantage of whole slide imaging technology.

The second objective is to break down the APW profile into a set of smaller, easier to implement building blocks, each of these focusing on one key aspect of the anatomic pathology digital workflow. The expectation is to collect sufficient feedback from all stakehoders of digital pathology (vendors, pathologists, institutions) in order to confirm and/or refine this set of profiles before starting to build them as new supplements to the Pathology and Laboratory Medicine Technical Framework.

Open Issues

• APW-EDM-01: Involve industrial offer for archiving and communication of whole slide images, as well as slide scanner manufacturers
• APW-EDM-02: Check the market for imaging modalities, PACS, and image reviewing and annotating software solutions, supporting the DICOM standard with the DICOM 122 supplement “Specimen Module and Revised Pathology SOP Classes” and the DICOM 145 supplement “Whole Slide Microscopic Image IOD and SOP Classes”

Closed Issues

• APW-EDM-03: Tissue microarrays may break the current specimen model. DICOM does cover this as a use case. Tissue microarrays are not used in clinical care, and so are left out of the scope of the profiles that will be derived from this white paper.

Use Cases

Use Case #1: Image Slides for Secondary Review / Consultation

Contributor assigned: Nicholas C. Jones

There are numerous contexts for consultation requests which have subtle, but important differences. Understanding these contexts and the pertinent variations for workflow are necessary to understand systems design, management, and operations for secondary reviews. (Temp Note: See NCJ's Consultation Workshop ppt from 2015 DPA conf for further details.) Terminology note: we will call the requesting party the requester, and the person fulfilling that request the consultant. Also note that all references to "second opinions" could also mean third, or fourth opinions, especially if the original primary/final diagnosis was in disagreement with the true second opinion.

(Note: most text moved to discussion page)

• 1.a. Pathologist requested consults, pre-primary diagnosis.
  • 1.a.1. Intrainstitutional: The pathologist is requesting a second opinion (through digital review) to another pathologist at their institution, either at the same site or another site in their network.
  • 1.a.2. Interinstitutional: The requester pathologist is requesting consultation from an outside hospital, usually due to the challenge of the case or the need for an external subspecialist.

• 1.b. Patient requested second opinion, post-primary diagnosis.

• 1.c. Physician requested second opinion, post-primary diagnosis

• 1.d. Second-opinion broker requests, post-primary diagnosis.

• 1.e. Legal cases, post-primary diagnosis.

• 1.f. Consultation for intraoperative interpretations of frozen section or rapid FNA slides.

Use Case #2: Immunohistochemistry Positive Control Slides

Contributor assigned: Raj Dash

Creating digital copies of immunohistochemistry positive control slides to preclude the need for creating multiple positive control slides for distribution to pathologists

• Request for IHC stain processed as usual
• Only one IHC positive control run per batch
• IHC positive control slides imaged and saved to network folder
• Positive controls NOT distributed ($$$ savings)
• Glass IHC slides reviewed by pathologist but same positive control reviewed digitally by all pathologists for a given IHC (i.e. only a single cytokeratin positive control slide even if requested across 10 different patient samples)
  • Note that this imputes the need to have one slide associated with multiple cases. This will be beyond most models of slide/database ontologies, so vendors are advised to design systems that can reference control slides to multiple cases. (NOTE FROM NCJ: Question for group- how do IHC labs normally document where the positive control slides come from? Should databases know that positive control slide x came from patient-case y, but applies to slides for case-set z? How should this be modeled? How do you do this in your lab, Dr. Dash? We should discuss in the teleconference.)

To be refined and continued.

Use Case #3: Managing Digital Assets for Anatomic Pathology Clinical Workflows

Contributor assigned: JD Nolen

These workflows include for instance, Whole Slide Images for Primary Diagnosis. Creating digital copies of all glass slides for primary diagnosis

• Specimen collected and transported
• Specimen gross exam with possible digital imaging and annotation
• Specimen processing
• Glass slides produced as usual
• All glass slides fed into high volume automated digital scanner
• Scanner tags images requiring manual intervention
• Digital images deposited in network share, VNA, or PACS
• Interface message to LIS sent as each barcode read off slide
• Acknowledgment from LIS indicates case is valid and ready for association with digital slide assets
• Additional message sent when slide digitization completed
• Interface message sent every time slide viewed or annotated

To be refined and continued.

Use Case #4: Sharing and Cooperating on Gross Examination Images

Contributor assigned: Laurent Duval

Definition: Grossing is the first step of sample preparation is macroscopic examination during which the sample is examined visually before microscopic examination.

Workflow: The process of grossing is performed in a meticulous and systematic fashion including all of the following main steps:

• Verify Specimen Labeling and Patient Identification
• Review Clinical Information
• Examine and Palpate All External Surfaces of the Specimen
• Understand the Resection Margins
• Inking Resection Margins
• Dissecting and Sectioning the Specimen
• Examining the Cut Specimen

Main Use Cases:

• Complex Specimen : Sharing and Cooperating on Gross Examination Images bring main value relies on complex specimens where anatomic details must be well understood before pathologists can make educated judgments about the extent of the patient’s condition and need for further resection.
• Pre Analytics: Another area would be around Pre Analytics Sample Tracking, when the sample collection might not occur at clinical site. Specimen fixation / transportation quality are essential for minimizing error rates and improving staining quality, and could guarantee a proper gross examination. Additional data to be considered for that purpose:
  • Tissue fixation quality (QC step)
  • Temperature tracker during transportation (data logger)

Gross Examination and Digitalization: Grossing tables with Image AND Voice recording devices make possible to record sample type, sub type, size and morphology, thus the macroscopy image and the related clinical data define the orientation for diagnosis.

• Request for cassettes can be also recorded at grossing step.

Pathologists could give a reliable diagnosis when microscopic images are coupled with macroscopic ones. In the era of the digitalization of pathology, it should be now possible to access micro and macro images / description from one place.

Interoperability: Need to consider a platform (ideally web) where sample images could be uploaded and be used as regular whole-slide images: they can be annotated, shared or even discussed via teleconsultation. Sample information recorded at grossing (sample description, pre analytics...) to be exchanged with HIS (Hospital Information System), APLIS (Laboratory Information System) and / or WAM (Work Area Manager), Middleware from medical devices company.

To be refined and continued.

Use Case #5: Incorporation of Legacy Digital Images for Use in APW

Contributor assigned: Raj Dash, JD Nolen, Dan Rutz, Anil Parwani

Legacy digital images may exist today in laboratories in a number of different file formats and include both still images (gross and microscopic) as well as whole slide images (microscopic only). File formats for whole slide images today include those originally produced by Aperio (.svs, .tif), Hamamatsu (.vms, .vmu, .ndpi), Leica (.scn), MIRAX (.mrxs), Philips (.tiff), Sakura (.svslide), Trestle (.tif), Ventana (.bif, .tif), and generic tiled TIFF (.tif). The DICOM standard for whole slide images reflects a hierarchy of tiles that allow for efficient transfer of data relative to both the source information and the destination display/device capability and requirements. DICOM facilitates association of patient and image metadata as part of a data "wrapper" around the actual image data.

With the implementation of an LIS, EHR, or image management system (IMS) or archival system (PACS or VNA), the bulk transfer of existing digital assets (DICOM and non-DICOM) will likely be required to facilitate at least rudimentary association between a patient, anatomic pathology tissue collection event, and various digital assets that might be available associated with that particular patient encounter. It is possible that the format of image data and associated metadata are in different formats during different time periods during which legacy information systems were utilized to manage the digital assets that exist in an organization as "legacy digital data". The value of this data will increase if future vended solutions recognize the need for association of this existing data with pathology "cases" and/or patient "encounters".

Due to ever-increasing prevalence of digital assets, consistent growth of information technology systems, and occasional turnover of LIS platforms, the need to maintain and incorporate “legacy” digital assets in laboratory pathology workflows will continue to be a necessary aspect of the full APW spectrum. Legacy migration will consistently come from multiple perspectives including: migration to a new primary LIS/digital cockpit, migration to a new image management system (WSI integrated solution, PACS, or VNA), addition of a new post-analytic system, and increasing scope of asset collection (biobanking, etc.). The legacy asset incorporation/conversion use case shares boundaries with a number of other use cases especially including consultation workflows, notably including: Incoming asset identifier management, Transfer of assets, replication of existing case structure and patient data, varying quality of source data that cannot be guaranteed. However, it maintains several unique features including the (relatively) massive scale of content covered compared to other workflows, potential value vs. complexity in handling internal audit & tracking data on historical cases, and the likelihood that nearly all organizations engaged in digital pathology practices will need to account for this situation regardless of their business scope and participation in other use cases. In particular, two of the central challenges to legacy asset incorporation are:

1. Identifier management (patient, case/report, specimen, block/slide/container, provider, user/technologist, physical labeling, etc.)

2. Replication of case structure, prior process & result data, and associated relevant patient information.

<to be continued>

Use Case #6: Image Analysis, Machine Learning and In Silico Workflows

Contributor assigned: Raj Dash

Data analytics and machine learning promise to provide significant value to those that embrace digital pathology workflows. Recent publications have demonstrated the capability of machine learning algorithms to fulfill complex diagnostic tasks, such as identification of lymph node metastases on digitized H&E images of lymph nodes¹. Some studies purport that these machine algorithms already have the potential to exceed the capabilities of human pathologists. For example, a laboratory information system (LIS) may allow ordering of analytic “tasks” on digital assets, similar to the paradigm in which immunohistochemistry might be ordered as tasks today in LIS platforms. In addition, LIS systems should be able to recognize when certain digital assets routinely require analytic tasks to be performed in a particular sequence as part of a digital “protocol”. For example as part of the routine processing of whole slide images acquired of sentinel lymph nodes of breast, the deep learning algorithm for metastasis identification might be run automatically immediately after whole slide scanning has been completed.

It should be permissible for these algorithm "tasks" to irreversibly modify digital assets through an annotation process as well as return metadata to store in to the LIS as a relevant diagnostic data point (e.g. Ki67 proliferation index for a region of interest), or finally create a dataset for further process by downstream "tasks" that are part of a larger "protocol".

¹Diagnostic Assessment of Deep Learning Algorithms for Detection of Lymph Node Metastases in Women With Breast Cancer, JAMA. 2017 Dec 12;318(22):2199-2210

Use Case #7: Quality Control / Quality Assurance and Error Correction Workflows to Support Digital Pathology

Contributor assigned:Nicholas C. Jones

Definitions: Quality Evaluation (QE): An assessment from a device, software algorithm, or person about the quality of a target physical or digital asset. Quality Control (QC): A system for verifying and maintaining a desired level of quality in an individual test or process. Quality Assurance (QA): Systemic monitoring of quality control results and quality practice parameters to assure that all systems are functioning in a manner appropriate to excellence in health care delivery. Specimen: A physical object (or a collection of objects) is a specimen when the laboratory considers it a single discrete, uniquely identified unit that is the subject of one or more steps in the laboratory (diagnostic) workflow. Container (Or Specimen Container): A physical object containing a specimen.

7a. Identification issues and ontologies for images. Any lab, APLIS, or Digital Pathology vendor should ensure first that they understand the identification processes, metadata ontologies, and troubleshooting requirements for digital pathology. (See discussion section for details.)

7b. Quality Evaluations for WSI

• Pre-processing: orders, identification, slide, tissue
• Scanning: Systems have internal analytics, sensors, and error-checking
• Post-scanning tech QE
• Pathologist QE
• Other personnel QE
• Image analysis QE

7c. Quality Evaluations for other pathology images

• Identification and association of images (i.e. gross image having correct metadata association/file name plus reference to case within the image)
• Order matching of images
• Pre-processing
• Imaging process
• Post-imaging QE

7d. Quality Control for Imaging processes - Systems, workflows, and protocols should detail all routine quality evaluations and workflow steps.

• At the most basic level: documents should specify workflow processes including all steps to evaluate and maintain quality
• Quality Evaluations (see above)
• Documentation: Imaging laboratory human made logs, scanner or server system logs, audit trail logs, reporting processes, interface engine logs or reports
• Calibrations: may include aspects like color calibration of scanners or monitors, periodic evaluation of staining/color representation of slides
• Troubleshooting worklists

7e. Quality Assurance for Imaging processes

• Design and documentation of workflows and quality control
• Explicit periodic analyses of operations and metrics for quality and results
  • These could include analysis of log files (via reports from systems), ST QE/QC metrics, pathologist rescan request rate, WSI deferral rates
  • Turn-around-time (TAT) analysis of processes
• Digital Pathology QA conferences
  • In initial validation or verification within a laboratory prior to clinical implementation, most validation studies/processes end with an adjudication panel of pathologists reviewing glass slides via microscope and WSIs to evaluate discrepancies/discordances between interpretations and determine root causes. These can be extended to include imaging and histology/lab personnel upon initial validation to help set quality control purposes for the laboratory.
  • Departments may wish to do periodic conferences to evaluate quality issues and improve quality control processes. This may be especially important for a feedback loop to laboratory and scanning personnel and iron out complex problems.
  • Many systems may allow for tagging images for QA review at a later time; this should correlate to QE/QC data.
  • There may need to be QA processes for sub-populations of tissue types, slide types, subspecialties, or diagnosis types.
• Aggregation for inspection for regulatory purposes - likely to include tracer cases, analysis of protocols, QE processes, follow up from prior inspections, etc.
  • Adverse Event Reporting - in some scenarios, groups may want or need to report adverse events of systems to vendors, FDA or other relevant outside groups.

7f. Quality Control and Assurance for Digital Diagnosis

• Randomized reinterpretation of digital cases via microscope. (Similar to cytotechnologist QC or regular surgical pathology QA processes.)
• Periodic re-verification/validation of image analytic results (i.e. occasional ordering of FISH evaluation to assert her2 image analysis functions are still achieving consilience)
• Randomized or periodic testing or auditing of equipment precision

7g. Quality Control and Assurance for Image Management, File Management, and Network Management

• Log file aggregation and analysis for systemic errors
• Random audit of tracer cases to verify image availability
• Monitoring of network load, network speeds, and other measures of network performance.
• System backups and auditing of file integrity (both for main archives and backups)
• Network security or vulnerability audits

Use Case #8: Digital Pathology in Support of Clinical Conferences

Contributor assigned:Nicholas C. Jones

Categories include:

• Consensus conferences
• Internal quality assurance conferences

Technical notes:

• It is commonplace for slides to be imaged for the purposes of such conferences. Workflows may vary in a primary diagnosis scenario.
• Although such conferences may use "thick clients" for WSI viewers, it may be considered more commonplace to use thin clients for such scenarios. As such, in a thick-client primary diagnosis setting, the determination of a set of WSIs previously scanned may warrant upload of scans to a thin client hosting server, or transmission from a file store or from one thick client to another. (This latter scenario could occur if a hospital used a thin client system for internal client cases, and a separate thin client system for telepathology cases received outside the hospital network.)
• To provide inter-operable vendor support for such conferences, it may be desirable to support modeling of sets of requests for multiple patients to pathology for the purposes of such conferences.
• Many digital pathology thin client systems allow for the organization of multiple cases, even for disparate patients, into sets or be indexed together in other forms, which can help assist in the process of organizing rapid, efficient, accurate switching between cases for multiple patients in these settings.
• While conferences are not generally tied to billing, from the perspective of cost accounting (saving multiple physicians time) they are extremely valuable. From the perspective of prospective clinical accuracy and providing constant feedback loops to and between clinicians, they are invaluable.

Use Case #9: Sub-contracting for special analyses on specimens

Contributor assigned: Gunter Haroske

Created as an increasing workload will be sub-contracted to special laboratories, e.g. for molecular analyses.

• Specimen collected and transported
• Specimen gross exam with possible digital imaging and annotation
• Specimen processing
• Glass slides produced as usual
• All glass slides fed into high volume automated digital scanner
• Scanner tags images requiring manual intervention
• Digital images deposited in network share, VNA, or PACS
• Interface message to LIS sent as each barcode read off slide
• Acknowledgment from LIS indicates case is valid and ready for association with digital slide assets
• Additional message sent when slide digitization completed
• Interface message sent every time slide viewed or annotated
• Case with all digital assets analysed by the pathologist
• Selection of relevant assets/slides/blocks for consultation or sub-contracting
• Mailing of relevant assets/slides/blocks to external lab
• AP reporting (preliminary)
• Mailing of the (preliminary) report
• Receiving results of consultation / sub-contracted tests
• critical reflexion
• AP reporting (synoptic, final)
• Mailing of the final synoptic report.

Use Case #10: Image Registration Functions

Contributor: Nicholas C. Jones

Image registration involves the creation of a cross-image coordinate system of multiple images for the same object(s) or "scene."

• 10.a. Image registration for swapping to correlated position on different slide from a single block.
• 10.b. Image registration for correlated multi-slide view from a single block. This allows for simultaneous presentation of multiple slides at once off the same block by allowing the user to control the location of one slide and having the system move the view of the other slides to the corresponding locations.

10.c. Image registration beyond just a series of serial sections of a block have been researched, and although these are (to our knowledge) not currently in clinical use, further possibilities have been documented in research environments.

Use Case #11: Digital Pathology in Support of Intraoperative Procedures

Contributor assigned: Raj Dash

Intraoperative consultations occur frequently to help guide surgical procedures and/or assess the diagnostic adequacy of tissue removed during surgical or a biopsy procedures. Typical staffing models to cover this type of clinical service generally involve a single pathologist supporting the needs of all operating rooms for a set period of time (usually 24 hours). This coverage model pragmatically allows for efficient use of limited pathologist resources. Situations often arise where this isolated individual may need to call upon the sub-specialty expertise of others. Rapid imaging of frozen tissue sections provides a mechanism for remove viewing by the pathologist on call as well as consultation from the primary pathologist to a sub-specialty pathologist. Requirements for digital histology imaging in this context requires rapid image acquisition (less than 15 minutes) and may require linkage to other data elements, including the gross image for orientation, clinical history, and procedural context (i.e. why the patient is undergoing a procedure and why tissue is being sent for evaluation). The whole slide image produced during intraoperative consultation may be at varying "levels" as the tissue is cut through to obtain a full thickness cross section and will almost always be accompanied with a deeper "permanent section" that represents the tissue remnant following standard histologic processing. Correlation between the frozen and permanent sections is a documentation requirement in most laboratories and usually occurs as the attending pathologist signing out the case reviews the final set of microscopic images.

Use Case #12: Digital Pathology for support of Anatomic Pathology Quality Control and Quality Assurance

Contributor assigned: Nicholas C. Jones and Nick requests assistance of a pathologist (Raj Dash volunteers but welcomes others)