Pursuit of an Optimized Surgical Workflow with Digital Pathology Integration

J. Mark Tuthill, MD Division of Pathology Informatics Henry Ford Hospital Detroit, MI 48202 [email protected]

Digital Pathology and AI Workshop Pittsburgh, PA December 13-14, 2019 Objectives

1. Understand digital integration prerequisites and opportunities 2. Present examples of operational systems used and digitally integrated at HFHS 3. Highlight common strategies the lead to success 4. Describe the integration of WSI 5. Recognize challenges and points of failure in digitial workflow and WSI Philosophical Hypothesis • “We can integrate AP workflow so that it models efficiency of the clinical laboratory” – What are the pre-requisites? – What is the low hanging fruit? • Sequence – What are the technology gaps? • Advanced robotics and pipeline development – Automation of manual processes Operational Systems

Digital Integration Information Technology

Lab Information System

PATHOLOGISTS TECHNICAL & SUPPORT STAFF Epic Wired Sunquest : Lab and CoPath Histotrak HLA MAS POC Syapse Aqueduct Hematology Lane Faxing

LAB PORTAL SCANNING APOLLO Digital Pathology Atlas ARCC Roche Scantron MikroScan − Surg Path Reqs − Store AP Req Scans Digital Cameras − Cytopath Reqs − Store Clin Path Req Scans − Clin Path Reqs − Integrate External AP Results − Outreach Documents − Telepath Integration HEALTHSTREAM − Associate Imaging to Reports Training (HFHS U) − Interface to acquisition devices Competency Cameras (1-2 M records/yr) - Gels LAB USER’S Molecular Pathology and NGS -Microbiology GUIDE pathology.hfhs.org/lug

TISSUE DOCUMENT BIOREPOSITORY CONTROL Master Control Clinical Pathology Systems Functional Areas Applications • Chemistry • SunquestLab • Hematology • SMART – barcoded specimen tracking, • Coagulation management. and archiving • >170 Instrument Interfaces via Sunquest • Urinalysis Instrument Manager (SIM) • Blood Bank • Autovalidation • Microbiology • Macroscheduler automated jobs • Serology • Histotrac: HLA laboratory system • Virology • MSQL Report Writer w/ Crystal • HLA • Results transmitted to EPIC • Molecular • Beckman Automation Line; Conexus; • Genomic Pathology Remisol • Point of Care – Glucometers >650 – Coagulation clinics Anatomic Pathology Systems

Functional Areas Applications • • Sunquest CoPath • Molecular Pathology • Biomaterial tracking system (BTM) – Illumina NGS • Scantron: requisition scanning • Cytology • mTuitive: synoptic checklists • Frozen Room • JFCC reporting via ePath • Autopsy • Barcoded LEAN production • CP Integration • Apollo Digital photography – Special Hematology • : Mikroscan – Flow Cytometry • WSI: Ventana Virtuoso, Mikroscan – Immunohistochemistry – Ventana Connect – Microbiology • Dako Connect • Tens of molecular pathology applications Other LIS Applications and Operations Functions • Atlas Portal: Outreach EMR; order entry and result reporting • Scantron: Document scanning for regulatory retention • LUG: Laboratory Users Guide • Lane Faxing: supports all Health system laboratory faxing • BTM: Tissue Biorepository • IT Service Now: Helpdesk; PI Change Control database for compliance • Apollo ARCC: Image storage integrated with both Sunquest systems (Lab & CoPath) • Cytovision Cytogenetics imaging system for Karyotyping and FISH analysis • Hologic Automated pap smear screening Road Map for Digital Workflow The Big Picture

• Pre analytic – Prior to receiving or analyzing the sample – Preparing samples for analysis • Analytic – The process of analyzing the tissue • Post analytic – The reporting of diagnostic information – Preparing for additional analytic studies Prerequisites for Anatomic Pathology Digital Workflow • Sophisticated electronic medical records system – Electronic orders interface for Anatomic Pathology • Bar code labeled assets with the laboratory – Assets with unique identifiers • Development of robotic technologies – *Grossing* – Embedding, Sectioning – Tissue transport – Sampling – Storage systems: cassettes and slides Prerequisites for Anatomic Pathology Digital Workflow • Electronic orders interface to the Anatomic Pathology Laboratory Information System (AP-LIS) – Similar to the clinical laboratory, a flow of orders to the LIS will enable: • Sample receipt • Tracking • Routing • Analytic Processing • Automation of several elements of case accessioning – Decrease errors – Increased throughput Prerequisites for Anatomic Pathology Digital Workflow • Bar code labeled assets within the laboratory – This is most essential early prerequisite to achieve automation within the laboratory – Bar coding of assets allows for: • Bar code driven workflow • Identification error reduction due to mislabeling • Improved efficiency by reducing manual labeling • Automation of subsequent activities – Integration whole slide imaging, interface devices – This is the key requirement for all automation Prerequisites for Anatomic Pathology Digital Workflow • Bar code labeled assets within the laboratory – Critical for each asset to have an unique ID embedded in the bar code – This will allow each block and slide to be managed uniquely supporting (Assets) • Sophisticated routing • Tracking of assets • Digital Pathology (unique ID on slides will be essential!) • Systems interfaces • Without uniquely identified assets the clinical laboratory could not have achieved the level of automation currently experienced Examples of Anatomic Pathology Digital Workflow

Real World Examples and Status Updates Examples of AP Digital Workflow

• Automation of histology orders (stain protocols) • Interfaced immunostain orders to automated immunostain platform • Bar code labeling automation – Automated production of cassettes at accessioning – Cassette driven generation of labeled slides • Tracking, routing and storage • Automated tissue embedding, Sakura AutoTEC • Automated microtome's Examples of AP Digital Workflow

• Automated block sampling • Automated slide sampling – Laser capture micro dissection • Conveyor belt systems, tubes, roving robots: routing • Slide collation robotics • Automatic diagnostics – Whole slide imaging algorithms for immunostains quantification – Automated pap smear readers Examples of AP Digital Workflow Histology Protocols • Automated ordering histology protocols for different sample types at case accession – When a particular part is accession the appropriate blocks and initial stain orders are generated – Initial billing fee codes are applied – Histology logs are electronically sent and printed providing early notification of work • This has increases efficiency and allows for LEAN processes – Work is standardized – Revenues were enhanced through better charge capture • This is not easy and required iterative re-work and constant attention to defects to get the most satisfactory end result Examples of AP Digital Workflow Real Time Labeling

• Essential first step to widespread AP automation • As previously stated the implications of bar code labeled assets drives all other processes • By themselves, the impact of automation of cassette labeling following by slide label generation are profound Barcode Specified Work Processes

1 This case is submitted in 3 specimen containers consisting of: part A - sigmoid colon biopsy, part B - transverse colon biopsy and 2 part C - stomach biopsy with standing preorder for Helicobacter pylori immunostain.

Protocol driven information is reflected in the 3 slide labels dictating 2 levels cut for each part.

The stomach biopsy protocol, part C, calls for an additional 2 blanks slides to be cut, 4 one for the immunostain & a 4th left unstained.

20 Outcome • With 'real-time labeling' the batch slide label printing process has now been entirely eliminated

• Specimen misidentification rates have been reduced

• Workflow efficacy in the histology lab has increased as cassette reading defects have been eliminated – Barcode reading defects required the histotechnologist to manually type in cases numbers, leading to increased risk of patient misidentification Results: Misidentification Rates

45 45 40 35 1.67% 30 25 20 0.62% 18 Number Mis-ID 15 10 Defects Percent of Cases 5 0.02% 0 1 Baseline Linear Bar 2D Bar Codes Codes (Jan. (June 2007) 2012) Examples of AP Digital Workflow Specimen Tracking and Routing • Allows us to record the location and status of specimen assets (parts, blocks, slides, etc.) as they are processed and move through the pathology laboratory • All components of a case can be tracked from when they are accessioned on through to storage or eventual disposal • Tracking allows for us to locate case assets and identify who has handled them and where assets have been (i.e. history) • I will not address routing and processing protocols as it applies to conveyance systems which we are not yet using Specimen Tracking Technology

AP-LIS: CoPath Plus v6.3 (Sunquest Information Systems, Tuscon, AZ)

CoPath Specimen Management Routing and Tracking (SMART) module

InfoMaker reports were created using PowerBuilder software (Sybase, Dublin, CA). SpecimenDesign Tracking • We defined specimen points of tracking (SPOTs) in the AP- LIS dictionary . Each SPOT is linked to a specific workstation as defined on the health system’s internal network

• As each asset is scanned and processed – location, scan time, status, and associated user data are automatically recorded

• Standard tracking tools allowed us to monitor assets in real- time AP Workflow Design *

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* Design: SPOT Implementation Histology Lab

Pathologists

• Currently 145 SPOTs have been defined Tracking Activities Tracking Reports

Asset Manager Asset Location Report

Specimen Discard Parts/Blocks/Slides at a SPOT

Specimen Tracking Update Parts/Blocks/Slides Aging Report

Slide Status Update Scan History Log

View/Update Specimen Tracking Specimen Tracking Scan Errors

Asset Reconciliation SPOT Turnaround Time Report

Unique ID Report

• Some functions are workflow specific while others can be utilized at multiple points in the process SPOT Turnaround Time Report

• Displays the time between when assets were tracked at one SPOT (i.e. Accessioning) to when they were tracked at the next SPOT (i.e. Grossing)

• This can be used to find out how long it takes assets to be processed from one workstation to another Workload Reports • Scan events can be tracked at individual SPOTS and users • Allows us to provide workload and productivity data for lab managers . Example: Slide counts by microtomy person Asset Reconciliation

• Allows the user to reconcile the assets in hand with the assets assigned to a case • Can be use iteratively – Gross – Accession – Embedding – Foldering

Examples of AP Digital Workflow Automated Platforms • Perhaps the most commonly automated process in the current AP lab – Including automated cover slipping • This saves hundreds of man hours per year • Has more consistent results versus manual staining and cover slipping • Digital interfaces with AP LIS will further enhance productivity and decrease errors Automated Immunostaining Interface Design • An HL7 interface was created between CoPath and the Dako autostainer Link 48 platforms – Allowed IHC orders placed in CoPath to be directly transmitted and received by the DakoLink instrument control software; used Dako labels • Our CoPath LIS was upgraded to version 6.0 which provided the capability to uniquely identify and track each case assets – Assign unique identifiers to each and every case asset (i.e. parts, blocks, and slides) – With this in place, unique slide IDs (linked to IHC orders in the AP-LIS) were transmitted to Dako autostainer control software – Dako autostainer instruments could then read and utilize native CoPath labels New workflow after deployment of the automated stainer interface

Slide are cut & labeled CoPath Interface Creates HL7 Slides placed Stains Ordered message onto instruments

Slide labels scanned

Slides IHC processed

Special stains CoPath – Dako New Workflow 1. Stains are ordered in CoPathPlus. 2. Stain orders are released to the interface on demand or scheduled. 3. Interface creates an HL7 message and delivers to Dako 4. Message is routed to instrument. Slide labels print from CoPath. 5. Slides are cut in the laboratory and Slide labels print from CoPath and labels are applied to slides. 6. Slides are placed into the instrument. Label is scanned by instrument which indicates the reagent stain workup. 7. Slides are processed. From CoPath Printer to Slides to Dako Bypassing Dako Relabeling Results

• With elimination of relabeling the slides and dual order entry through automation markedly decreases assay run time – This saves upward of ~700 hours of manual effort per year while eliminating errors, improving patient safety and improving laboratory throughput • Increases order accuracy by reducing keystroke errors. • Enhances operational efficiency by automating processes. • Enforces safe, consistent, efficient handling of specimen. Examples of AP Digital Workflow Digital Pathology • Not just whole slide imaging! (WSI) • Distributed microscopic images • Distributed EM • Gross images • Scanned documents • Image analysis • Clinical lab images: gels, plates, hematology analyzers • Cytogenetics analysis • Digital Pathology is: – digitally capturing, storing, moving, analyzing, interpreting tissues (and other assets) submitted to the laboratory for the purpose of diagnosis, clinical communication, documentation and quality assurance Apollo ARCC Implementation • Apollo ARCC Image management provides: – Expandable EMC SAN based storage – Thin-client, web services based deployment – Management for all existing image-generating devices – Disk and network monitoring – Security management for users • Permission-based logon, very nuanced • Thick-client and Thin-client access – LIS integration • Interfaces for ADT and images • Images to be send to the EMR via AP-LIS (CoPath) – Sophisticated device integration including interfaces and file mover services

TECHNOLOGY

File mover services leveraged

Apollo ARCC Grossing LIS Integration Autopsy stations Autopsy suite suite

Specimen Robotic Document X-rays Telepathology Scanners Final Workflow • Cases accessioned into CoPath – ADT sent to Apollo • Images acquired for case automatically stored in Apollo • Images “links” are sent back to CoPath (or not) as “results” – Those returned are configurable: • Associated with the case • Embed into the report • Images viewable in Apollo or CoPath • Report send to EMR with or without images as desired Examples of AP Digital Workflow WSI: Drivers for HFHS

• Maturity of the WSI technology platforms – Improved performance – Decreasing costs • The need for a distributed digital pathology workflow to support diagnostic studies – Move images not glass! • Loss of support for our robotic telepathology platforms • The desire to adopt cISH and image analysis for diagnostic panels Decisions and Goals • Stand up technology to replace robotic telepathology – Selected Mikroscan as a vendor • Stood up four D2 systems in each hospital to allow for telepathology support of intraoperative consultation • Select WSI partner for cISH analysis and distributed diagnostic imaging – Selected Ventana Roche as a partner • Implement iScan Coreo and Coreo HT platforms • Interface these platforms with Sunquest CoPath • Validate the Ventana Ultra cISH platform • Harmonize bar code labeling symbologies so that CoPath generate bar codes labels would be used • Integrate this technology into CoPath and Apollo workflow TECHNOLOGY

File mover services leveraged

Apollo ARCC Grossing LIS Integration Autopsy stations Autopsy suite suite

Specimen Document X-rays Whole Slide Imaging Scanners Prerequisites for Interfacing WSI • Requisite hardware and software for WSI capable of using HL7 messaging – Network attached storage solution – Network bandwidth • We had WSI in place since January 2016 • An LIS capable of communicating with WSI systems via HL7 • Electronic histology orders used for all histology processes • Bar code labeled assets with unique ID’s Value of Interfacing WSI • Immediate case access by pathologist – No annotation • Significantly more data is populated – Part, Block, stain – Patients details: age, sex, DOB; – Assigned pathologist • Leveraging bar code technology • Case available to pathologist immediately upon successful scan – No need to annotate and release iScan HT Digital Workflow • Cases are created in CoPath at accession • HL7 message is sent to Ventana Connect and onto Virtuoso • Slides cut, stained and placed on HT for scanning • Scanned images automatically associated with patient, CoPath accession and pathologist • Scanned images viewable through CoPath interface • Select fields can be exported and integrated into the CoPath report using Apollo EPMM LIS Workflow Integration Examples

Launching WSI from your LIS LIS Integration • All gross images and images captured from cameras mounted on microscopes go into Apollo ARCC and can be sent directly via HL7 interfaces to pathology reports, then onto the EMR embedded in PDF’s – The include Scanned documents, EM, and X-ray (Faxitron) images • WSI is a completely different imaging stream – WSI for a pathology cases can be launched from • CoPath LIS • WSI image viewer (Roche Virtuoso) • Apollo Enterprise Viewer (soon to come) • The LIS is the integrator – All images can be opened from CoPath on a case by case basis • This is the basis of the true next generation pathology workflow – Examples….

Challenges and Points of Failure Overall Challenges • Pathologist workstation – Multi monitor solutions, form factor obsolescence – Desktop computing upgrades and rollover’s – Real estate in offices • Bar code production stability – New devices – New printers – Bar quality monitors Overall Challenges • Form factors constantly changing and varying – Slides, coverslips, racks, trays, labeling, bar codes • Slide Handling variations • Loading process impacts run times – Continuous versus batch • Overall system durability – Preventive maintenance – Downtimes, redundancy – System monitors Overall Challenges • Security and configuration – Multi user profile versus single account • Interoperability and proprietary file formatting • Interfaces: Instruments, LIS, HER – Maintenance, cost • Automation – How to must effectively connect systems? – Conveyance – Storage of assetts Gaps in LIS-WSI Integration • Workflow – Launching of images • Window targeting • Inside or outside of application – Work list • Priority • Status: quality etc • Notifications – Security hand off between systems • LIS versus image management system – Image integration into pathology reports Gaps in LIS-WSI Integration • Image management – Storage – Retention – Purging – Updates to the cases: insertion of new images, deletions of old – Case Corrections – Rescan requests – Acceptance criteria Gaps in LIS-WSI Integration Instrument Controller vs. LIS • Scanning process – Thumbnailing vs. not – Identification of errors – Error management communication – Run management – Continuous flow – Impact of fatal errors Summary

Realizing Effective Digital-Enabled Anatomic Pathology Workflow Summary Realizing Effective Digital-Enabled Anatomic Pathology Workflow • Many aspects of AP can be digitally integrated – More integration is available than meets the eye – We don’t count some of these that have a big impact • Digital integration saves time, money and improves patient safety • Very few gaps in robotic solutions remain – Gaps will close – Pricing will come down • Build upon your foundations: sequence carefully! Questions?

J. Mark Tuthill, MD Division of Pathology Informatics Henry Ford Hospital Detroit, MI 48202 [email protected]

Digital Pathology and AI Workshop Pittsburgh, PA December 13-14, 2019