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.

• 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. In the case where the pathologist was already viewing the slides digitally (primary diagnosis), this would likely be in the same system (i.e. uses synchronous or asynchronous consultation functions within their IMS/PACS). This is likely due to the case being challenging, or otherwise meriting the review of a sub-specialist (or different kind of subspecialist, such as a gyn-specialist requesting the opinion of a dermatopathologist's consultation).
    • Note that this may or may not trigger requests for scans, would not trigger billing for the patient, but may trigger records or documents internal to that organization for tracking consultation between pathologists within the organization.
    • Note that due to the internal nature, it can be assumed the consultant will have access to all electronic documentation (EHR, APLIS, etc.), but that there are likely to be either text based messages and annotations (for asynchronous consultation) and/or verbal communication between requester and consultant in the case of synchronous consultation.
    • Much of the value of this process centers around efficiency (compared to glass slide processes) is in limiting "phone or email tag" issues, maximizing communication ("this ROI is what worries me"), and generally improving organization and documentation of the process.
  • 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.
    • Slides may need to be scanned if the requester was using the microscope. The requester pathologists may only request a subset of the slides to be scanned (i.e. if 9 slides are normal, and 2 are questionable, they may scan and send just the 2 questionable slides to the consultant.) Note that in this context, the scanning processes will likely be considered high priority or rush requests; systems should allow for differences in priority of scan requests.
    • The request to the consultant will be coupled with consultant's summary of the patient's clinical history, notes and questions (i.e. "is this a microfocus of carcinoma?" or "my differential is diagnosis A vs diagnosis B.") along with printed or saved documentation (i.e. preliminary report including items like frozen section or rapid fine needle aspiration interpretations, reports from surgeons or radiology imaging processes, other images from AP processes such as gross images, IF, EM, etc.) and possibly blocks. Inclusion of profiles like APSR here will be highly beneficial, especially if APSR profiles support itemizing both all assets that exist on a case as well as what was sent for consultation.
    • Note that the consulting institution will need to match images to clinical history and documentation. The consulting institution may also have quality control procedures to check image quality, and may need to troubleshoot the process by asking for rescans or other clinical information.
    • There are potentially significant differences in process here based on how image distribution and viewing are intended to function. This may involve uploading WSIs and other data to a thin client host, uploading data to a repository for download to the consultant group, or sending disks (i.e. flash drives or DVDs) with the data.
    • Much of the value proposition in this process revolves around reducing turn-around-time of processes versus mailing glass slides, further coordinating the consultation process (which requires some collaboration between the requesting site and consultant site), and improving on the consultation product to the requester (i.e. requester gets the consultant's report in the end, but can also see annotations or other notes to see in more detail why the consultant interpreted the case in such a way). These value propositions also merit noting that sending physical media can potentially be viewed as "the worst of both worlds" if they require both imaging processes and still have the long shipping time related issues and risks.
• 1.b. Patient requested second opinion, post-primary diagnosis.
  • These contexts can be generally assumed to be going to a different institution. While there may be less pressure on the original institution for timeliness, the patient may be waiting on making a treatment decision based on the second opinion, so process turn-around-time is still very important. But because the patient is likely requesting the review sent to a specific institution or other pathologist, it should not be assumed that there is a functional telepathology pipeline between the two institutions.
  • If there are no specific instructions accompanying the request (other than send this case X to institution/pathologist Y for second opinion), the onus is on the institution sending the material to gather materials (documents, images, scanned slides) for send out. The original hospital may wish to image some or all cases for such send-outs either to archive such materials (to mitigate risk of slides being damaged or lost in transit by having digital copies), or to prevent such risks by sending WSIs instead. There may be less benefit of this process context to the consultant pathologist or institution (other than mitigating risk of damage or loss of glass slides) unless workflows are set up to improve turn-around-time, organization of data, or some other benefit to the consultants. It is important to consider the consultants as stakeholders in these processes as well.
    • Again, exact processes will vary based on image distribution (i.e. whether WSIs and other clinical data are made available for download, sent via physical media such as DVDs, or other methods).
• 1.c. Physician requested second opinion, post-primary diagnosis
  • These requests usually come from (non-pathologist) physicians prior to making treatment decisions with the patient. Some physicians (such as oncologists) do this routinely for all new patients, as even a low probability of changing the diagnosis can yield huge value for the patient by preventing unnecessary or inappropriate treatments.
  • It is common for the physician to request the second opinion be sent to the their institution (especially common in academic medical centers, as the clinician may interact with the patient on tumor boards or future biopsies or excisions), or have preferred consultants outside their institution (more common in smaller institutions). Retaining images of prior slides are of significant clinical benefit to pathologists that will review future biopsies or excisions for the patient, as glass slides are generally sent back to the original institution within a specified timeframe.
• 1.d. Second-opinion broker requests, post-primary diagnosis.
  • These are a hybridization of 1b and 1c. Patients may request the services of second opinion brokers to organize consultation on all of their case, including pathology but also radiology, oncology, and other areas. The second opinion brokers provide case management services, and may delegate different aspects of the overall consultation to different groups.
  • Differences in the organization of these processes merit their mention here, as the group managing the consultation is external both to the original diagnosing institution and the consultant pathologists. Workflows and data pipelines may either go through the second opinion broker's systems or otherwise need to be coordinated with the second opinion broker organization who act as proxies on behalf of the patient.
• 1.e. Legal cases, post-primary diagnosis.
  • In these cases, imaging may occur to archive the case prior to glass slide send-out for consultation, or to send out the images to legal teams which will seek consultants.
  • Workflows for legal cases are significantly different than clinical processes, but may be less urgent (for clinical care purposes) than other contexts discussed above.
• 1.f. Consultation for intraoperative interpretations of frozen section or rapid FNA slides.
  • This should be clearly delineated from use case #11 as those individuals requesting a second opinion. (I believe this is done in at least Canada for neuropathology frozen sections.) Such workflows would need to be very fast (if the patient is under anesthesia, the slide was already made, and a first pathologist already consulted) and thus may require special extra steps like pre-communicating the possibility of a required consultation, bypassing other normal administrative processes to get the images to the consultant immediately, and/or receiving verbal interpretations over the telephone during consultant visualization.

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: JD Nolen, Dan Rutz, Anil Parwani

TBD

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. Notes on identification and QE ontologies: With the exception of in vivo microscopy (beyond the scope of this IHE White Paper, and in this regard, closer to Radiology's paradigm), we should consider the scene or target of an imaging process as a (potential combination of) specimen(s), container(s), and other components of the container(s).

• A bag(container) with a sticker with patient's information (component of bag container) is received at the surgical pathology laboratory. It holds two jars(containers) and in an outer pocket a folded paper requisition which also has a sticker with the patient's information. The requisition is considered a separate object, though it correlates to the specimens in the container.
  • Between the requisition and the jars, the case is accessioned as case SYY-X. The requisition is labeled with the pathology case number SYY-X. If the requisition gets scanned, it should be associated at the case level (for the APLIS), and if put into DICOM format, it would fall under the secondary capture IOD.
  • One jar(container) holds formalin and biopsied tissue (specimen). The jar's sticker has the patient information and "LEFT BREAST 6:00" written on it.
    • Once the case is accessioned, the first jar becomes part A of the new case. The core biopsy is embedded in a block (new specimen, parent of the core bx 6:00-specimen A) labeled as A1.
      • Four slides(containers of new subspecimens) are made from block A1: A1-1,2,3, and 4. Their parent is block A1.
        • Each of these slides is later scanned. Slide A1-3 had a tissue fold which contributes to the the first of two tissue sections on the first scan to be out of focus, so the technician rescans it. The second scan has the has the first tissue section of slide A1-3 in focus, but then the second tissue section of the slide out of focus. In the interest of time, the technician makes annotations on the slides for the pathologist to reference the first scan of A1-3 for one part and the second scan of slide A1-3 for the second. (Note the importance: you may want to keep two scans of the slide. Slides:scans is a 1:n relationship.)
  • The other jar holds a core biopsy specimen and is labeled "RIGHT BREAST 3:00."
    • The second jar becomes part B in the case. The right breast core biopsy is embedded in block B1.
      • Four slides are made from block B1: B1-1,2,3, and 4. Their parent is block A1.
        • All four slides are scanned successfully.

For ease of understanding: quality evaluations could occur for any of these objects at any step in the diagnostic process as part of the greater system of quality control.

• Accessioner/preprocessing QE could note a problem at the receipt part prior to case accession. (Missing or misprinted label, for instance, or an order/delivery problem: perhaps it was a fine needle aspiration biopsy, the bag needs to be delivered to the cytopathology laboratory instead.) Since the white paper's topic is the digital aspects of this, we will skip over most normal processes here. The important point is that we keep the model of the evaluator making a quality evaluation of the target (specimen, container, requisition, etc.) at various points in the process, and each problem could become resolved, generate a warning/advisory, or be unresolvable (i.e. receiving an empty specimen container, which might not generate a surgical pathology case number, but certainly should generate a safety report or other QA trigger).
• So it is important to understand that images could be taken of various targets here:
  • An image of the bag with containing the jars and requisition could be taken to document quality processes (i.e. a half-printed barcode on the label) by a basic camera modality. In this instance, you had an accessioner's QE of the bag trigger a warning (only 1.5 matching labels instead of 2), so the image is taken to document that issue.
    • A specimen could be imaged during grossing and sectioning, resulting in a gross image.
      • The block itself could be imaged, perhaps after microtomy, but prior to being sampled for a molecular diagnostics test. (The block itself could also be imaged after a subsection was removed to document the location of the sampling of the molecular test.)
        • A slide could be imaged in numerous ways:
          • photographed macroscopically by a scanning technician to document that the slide has a large chip/piece missing from it, and that it cannot be scanned in the whole slide scanner.
          • The scanner takes a macroscopic image of the slide to separate the slide label area, and to analyze the coverslipped area for contrast and thus which areas of the slide to scan.
          • The slide is scanned by the scanner, which stitches together micrographs into a WSI, saving them along with metadata and the macro image. Note that the slide could have multiple scans from the same scanner, with the same or different scanning settings, or from different scanners, or pre-destaining and post-destaining. Furthermore, slides can be cut and left unstained for later staining; processes between APLIS and digital pathology systems should include for "update" messages such as a slide being stained, unstained, or restained, or additional slides being cut from the block.

It also must be noted that slides relationships vary:

• Slides with formalin fixed, paraffin-embedded tissue sections generally have the relationship of Patient->(Case/Container)-> Part-> Block-> Slide.
  • Section thicknesses can vary (i.e. 5u vs. 3u) and may affect scanning procedures or success rates.
• A liquid based pap smear would have a different relationship Patient->(Case/Container)->Vial (i.e. Surepath or Thinprep vial)->(Tube, which may be implicit)->Slide.
• A direct smear of a specimen could be Patient->Excised tissue (pre-container)->direct application to slide.
• Whole mount or otherwise larger slides should be modeled in the system. (Some scanners can accept "non-standard" slide sizes, and others cannot.)

Optimal databases and information processes will correctly model different types of slides.

7b. Quality Evaluations for WSI

• Pre-processing QEs
  • Scanning Technician(ST) Orders QE (scan order vs. slide type vs. request/reason type vs. priority vs. location vs. presence of existing scans)
  • ST Slide QE: physical problems with slide? (Resolvable or not? Change scanning process or not?) Issues with tissue? (i.e. note presence of air bubble, tissue folds, possible necrosis warranting extended focus, etc.) Fingerprints, dust, extra mounting media on slide? (Can it be cleaned off or not?)
  • ST Identification QE: Identification issues? Identification exceptions warranted? Or ID based rejection?
• Scanning QEs: initialization and during scanning process
  • Scanner QE for robotics/physical issues- sensors check for robotics issues, check for correct placement of slide on stage
  • Scanner QEs for macro image capture or equivalent step (including label/barcode capture)
  • Scanner QEs for tissue

Scanner-Slide Quality Evaluation

Scanning Software image quality evaluations

Scanning technician image QE

(Still working on this - NCJ)

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

Contributor assigned:Nicholas C. Jones

NCJ Question 1: How do we want to define clinical conferences? I would like to avoid the ambiguity of definitions like this. It may be easier to define through sub-types and examples, which is the approach I'll tentatively take here. But I would definitely like to discuss the tentative definition I'm suggesting here

Tentative definition of clinical conferences(for discussion): meetings of two or more clinicians and/or other clinical personnel, either in person, through tele-presence, or a combination of physical and tele-presence, to discuss and review clinical details of one or more patient's cases for prospective quality control purposes or retrospective quality assurance purposes, within the domain of clinical care for the patient. This does not include academic case studies in settings such as a professional association meeting. Clinical conferences are generally scheduled, as opposed to ad hoc processes, which would more commonly be considered consultations.

Categories include:

• Consensus conferences: common term used for routine conferences in which pathologists review one or more challenging or rare cases with colleagues prior to sign-out. Such conferences may or may not be noted in the final diagnosis of the report. Consensus conferences could occur at a multi-headed microscope, through tele-presence using static, dynamic, or whole-slide images, or any combination of imaging techniques.
  • In a multi-site/enterprise setting, consensus conference through digital pathology may be desirable as conferencing pathologists could be distributed geographically, and digital pathology supporting such conferences can allow for easy, efficient review of pathology images for group review.
  • In some circumstances, we could expect the desired combination of multi-headed microscope use along with digital pathology, such as in the scenario of prior consultation cases which were digitally archived needing to be reviewed along with glass slides at the multi-head. Alternatively, in a primary diagnosis setting, we may expect current cases would be reviewed through digital pathology systems being coupled with glass slides of prior cases (pulled prior to conference, but not scanned) being reviewed at a multi-head.
• Internal quality assurance conferences: Within a pathology department, certain cases may be retrospectively reviewed on an ad hoc and/or systematic basis. For instance, a cytopathology/histopathology QA conference might review cases in which the cytology and histology diagnoses disagreed to find root causes. (Such as issues of interpretation versus issues of sampling variation in cases involving fine needle aspiration biopsies and core biopsies.)
• Tumor boards or multidisciplinary conferences: In these settings, clinicians of multiple specialties review cases together. (Note we may make the distinction between tumor boards and multidisciplinary conferences as in some cases the patient may not have a tumor, yet the case can still warrant a multidisciplinary conference review.) In many instances, these conferences may occur outside the pathology department, so pathologists may traditionally show static images (or commonly a powerpoint with multiple static images), projections of a slide from a microscope, or whole slide images. Note that it is common for radiologists to use thin client viewers to present radiology images, so toggling to thin clients to present whole slide images is often considered highly desirable for such conferences. As the complexity of physical organization of clinicians and interconnected work grows, flexibility in presentation of such conferences is highly valuable to provide for clear, efficient presentation of case materials to ensure high quality conferences that minimize time-related switching costs in such 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. Common current practice may involve one or more parties communicating to pathology the request to review cases at the next conference by e-mail, but it may be preferable to allow for systematic requests (i.e. through the EHR) from parties like oncologists to pass from the EHR through interfaces to other systems (APLIS, PACS, and/or digital pathology systems) to assist in administration of such conferences. (Note from NCJ: Do we want to discuss what these orders might look like as HL7 messages? Does anyone know of examples of this?)
• 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."

• Example for explanation: since many liken WSI to GoogleMaps, let's use GoogleMaps (used here as GoogleMaps + Google Earth functionality) as the example for analogy. Both WSIs and GoogleMaps involve the creation of numerous individual images through an optical and camera system. WSIs involve capturing numerous micographs (each a mosaic of pixels) in a mosaic pattern of micrographs, stitched together, while GoogleMaps took numerous satellite images of the Earth and stitched them together. But GoogleMaps also includes complex image registration algorithms, where images from space were correlated to images of the earth (various types of maps) to create a more complex but more accurate model of the Earth. Together, they allow for easier use of more complex path creation, but also to toggle in a location between a "street map view" and the satellite view of the same location. Image registration functions are used in other areas of medical imaging to correlate multiple modalities of imaging for the same organ(s).

• 10.a. Image registration for swapping to correlated position on different slide from a single block. This feature allows for the user to swap to another slide from the block (i.e. going from A1-1 H&E to A1-2 CK8) to the analogous location on the new slide without the need to visually search for it. Used in a larger series, it allows for oscillating between multiple slides in the same location (ie. A1-1 H&E, A1-2 CK8, A1-3 CK 14, A1-4 ER, A1-5 PR, A1-6 her2... etc.)
• 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. (Note: "manual" control/locking of multi-slide views is basically similar here but is not using an automated image registration system to create the alignment of views.)

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. These include creating 3D virtualizations of blocks by registering large series of WSIs, or registration of multiple blocks with gross images and through those to other images such as those from radiology. Vendors, academics, and standards may want to consider these more complex image registration as future possibilities and thus design ontologies and systems that are extensible enough to warrant these use cases in the future.

Note that in the case of doing image registration in multiple slides, this may be considered a loose definition of image registration, as technically the different slides could be considered different "scenes" as a different object is being imaged. But since the slides are different serial sections cut off an FFPE block, it is ideally very close to the same scene (with ~5 um or even less between serial sections). Still, that difference between the slides makes these image registration processes more challenging, as variations between the levels off the block will show small variation in shape, size, and features from other slides.

• It is important for the success of such algorithms for systems to pass identifying metadata not just on unique slide identifiers, but also slide section thickness (such as 5 um), block identifiers, and tissue cut order (i.e. A slide called "A1-7 H&E" on the label may mean the 7th slide off the block "A1," but its unique identifier may not itself indicate that this slide is the 7th off the block, especially if the APLIS unique identifiers are created automatically in the database by order of their creation as a database asset rather than physical cut order.)
• Furthermore, tools for manual intervention to change orientation of tissue may be required to aid these algorithms. For instance, original H&Es may have been cut with epidermis facing in one direction, while the subsequent cuts for IHC may have a different orientation. Tools to permanently rotate images in multiples of 90 degrees, or temporarily rotate images to aid in image distribution may assist in these processes and be part of active troubleshooting, as image registration may be done on-demand by technicians prior to passing WSIs onto pathologists.

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

Contributor assigned: Raj Dash

Such as frozen section interpretation and rapid fine needle specimen adequacy assessment.