Post on 24-Sep-2020
Selecting the Optimal Digital System for Your Department Based on Case Volume and Projected Uses
Ulysses G. J. Balis, M.D., FCAP, FASCP, Fellow AIMBEProfessor of PathologyDirector, Division of Pathology InformaticsDirector, Computational Pathology Lab SectionDepartment of PathologyMichigan Medicineulysses@med.umich.edu
Faculty Disclosure
Advisory Board: Inspirata, Inc.
Plateau of ProductivitySlope of Enlightenment
Trough of Disillusionment
Peak
of I
nfla
ted
Expe
ctat
ions
Innovation Trigger
Phase
The Hype Cycle as Witnessed within Digital Pathology
Time
Expe
ctat
ions
Deep Learning All-digital Whole Slide Imaging Workflow
Specific DP Reimbursement Models
High ThroughputScanners
Digital Consultation Outreach
Mul
tiple
x as
says
FDA Clearance for Primary Diagnosis
QuantitativeImmunoscoring
Info
rmed
Det
ectio
nConventional MachineLearning
NLP
DICOM
Liqu
id B
x
Effective Federated Integration with AP-LIS systems
Digital Pathology System Configuration
Strategic Considerations Selection of a portfolio of scanning appliances, matching device capabilities to intended
use cases
Determination of storage needs and storage strategy
Computational requirements, both onsite and offsite
Tactical Considerations (also important but covered elsewhere in this workshop) Funding model
Physical Space and device colocation
Workflow
Equipment recharge/refresh model
Interoperability
Scanning Platforms – An overview
Scanning instruments have evolved through at least four major generations since commercial availability in 2001 (Aperio T1), with improvement seen in: Scanning speed
Image quality
Batch scanning capacity
WSI scanning appliances are now largely commoditized, with a growing number of models now slated for near-term FDA approval
Contemporary scanners, while far-superior to original offerings, still have opportunities for improvement in: Speed
Point spread function
Scan to view timing latency
Capture of additional optical modes besides brightfield (Z-stack, fluorescence, phase contrast, polarization, hyperspectral, just to name a few)
Workflow (pre-, analytical, and post-analytical)
Ease of integration with host AP-LIS systems and image interoperability
3DHistech
Hungarian company based in Budapest; founded in 1996 First European manufacturer of full turn-key solutions for WSI scanning Added expertise in tissue microarray management Significant Software portfolio Added offerings in Pathology Workflow
Digital Pathology
Frozen Section
Gross Examination
Remote Consultation Portal
Tumor Board Module
Numerous Educational solutions Scanner exhibit superb mechanical and optical design
3DHistech - Pannoramic DESK II (DW)
Entry-level low volume, single slide scanner
Default single-objective magnification of 41x ( 26x and 90x options)
1x3 inch and 2x3 inch slide (DW) capability
90 second scan time at 26x (15mm*15mm)
No fluorescence capability
No Z-stacking
Requires external PC to drive instrument
3DHistech - Pannoramic MIDI
Intermediate level, low volume, 12 slide scanner Two-objective design with default magnifications of 26x and 41x
Optional 90x brightfield Optional 20x, 32x, and 64x for fluorescence
1x3 inch only slide capability 90 second scan time at 26x (15mm*15mm) Fluorescence capability No Z-stacking Requires external PC to drive instrument
3DHistech - Pannoramic SCAN II
Intermediate level, moderate volume, 150 slide scanner Two-objective design with default magnifications of 26x and 41x
Optional 90x brightfield Optional 20x, 32x, and 64x for fluorescence
1x3 inch only slide capability 90 second scan time at 26x (15mm*15mm) Fluorescence capability No Z-stacking Requires external PC to drive instrument
3DHistech - Pannoramic 250 Flash II
High-volume, intermediate speed, 250 slide scanner
Two-objective design with default magnifications of 26x and 41x Optional 52x brightfield
Optional 20x, 32x, and 64x for fluorescence
1x3 inch only slide capability
36 second scan time at 26x (15mm*15mm)
90 second scan time at 40x (15mm*15mm)
Fluorescence capability
No Z-stacking
Requires external PC to drive instrument
3DHistech - Pannoramic 250 Flash III
High-volume, high speed, 250 slide scanner Two-objective design with default magnifications of 26x and 41x
Optional 52x brightfield Optional 20x, 32x, and 64x for fluorescence
1x3 inch only slide capability 20 second scan time at 26x (15mm*15mm) 60 second scan time at 40x (15mm*15mm) Fluorescence capability No Z-stacking Requires external PC to drive instrument
3DHistech - Pannoramic 1000 (P1000)
High-volume, high speed, 1000 slide scanner (up to 100 slides/hour)
1x3 inch and 2x3 inch slide capability with native slide stainer basket support
Intended to support high-volume, primary DX setting (FDA certification pending)
0.25 micron pixels at 40x
Fluorescence capability
No Z-stacking
Requires external PC to drive instrument
3DHistech – Other Systems
Pannoramic Confocal
Pannoramic Midi II
Roche Ventana DP200 (DP_XXX Pending)
Intermediate-volume, intermediate-speed, 6 slide scanner
One-objective design with default magnification of 40x 0.23 micron pixels at 40x
1x3 inch slide capability
No Fluorescence capability
True Z-stacking capability
Integrated Digital Pathology Workflow Solution with extensive capabilities
Requires external PC to drive instrument
Hamamatsu NanoZoomer SQ
Low-volume, low-speed, single slide scanner One-objective design with default magnification of 20x
0.23 micron pixels at 40x 0.46 micron pixels at 20x
1x3 inch slide capability 150 second scan time at 20x (15mm*15mm) 275 second scan time at 40x (15mm*15mm) No Fluorescence capability True Z-stacking capability Requires external PC to drive instrument Exceptionally precise slide scanning mechanism
Hamamatsu NanoZoomer S60
Intermediate-volume, intermediate-speed, 60 slide scanner 30 slide capacity with 2x3inch option
One-objective design with default magnification of 20x 0.23 micron pixels at 40x 0.46 micron pixels at 20x
1x3 inch and 2x3 inch slide capability 60 second scan time at 20x (15mm*15mm) 150 second scan time at 40x (15mm*15mm) Fluorescence capability as an option True Z-stacking capability Requires external PC to drive instrument Exceptionally precise slide scanning mechanism
Hamamatsu NanoZoomer S210
High-volume, intermediate-speed, 210 slide scanner One-objective design with default magnification of 20x
0.23 micron pixels at 40x
0.46 micron pixels at 20x
1x3 inch slide capability only 60 second scan time at 20x (15mm*15mm) 150 second scan time at 40x (15mm*15mm) No Fluorescence capability True Z-stacking capability Requires external PC to drive instrument Exceptionally precise slide scanning mechanism
Hamamatsu NanoZoomer XR
High-volume, high-speed, 320 slide scanner One-objective design with default magnification of 20x
0.23 micron pixels at 40x
0.46 micron pixels at 20x
1x3 inch slide capability only 35 second scan time at 20x (15mm*15mm) 45 second scan time at 40x (15mm*15mm) Fluorescence capability as an option True Z-stacking capability Requires external PC to drive instrument Exceptionally precise slide scanning mechanism
Huron TissueScope PE
Low-volume, low-speed, Two or 1-slide scanner 1 slide capacity when loading 2x3 slides
Two-objective design with magnifications of 20x and 40x 0.25 micron pixels at 40x
0.50 micron pixels at 20x
1x3 inch and 2x3 inch slide capability 300+ second scan time at 20x (15mm*15mm) 300+ second scan time at 40x (15mm*15mm) No Fluorescence capability No Z-stacking capability Requires external PC to drive instrument Exceptionally well-designed optical pathway with very uniform lighting
Huron TissueScope LE
Low-volume, low-speed, 12 slide scanner 6 slide capacity for 2 x 3 inch slides
4 slide capacity for 3x4 inch slides
2 slide capacity for 4x5 inch slides
1 slide capacity for 5x7 inch slides
1 slide capacity for 6x8 inch slides
Two-objective design with magnifications of 20x and 40x 0.25 micron pixels at 40x 0.50 micron pixels at 20x
300+ second scan time at 20x (15mm*15mm) 300+ second scan time at 40x (15mm*15mm) No Fluorescence capability No Z-stacking capability Requires external PC to drive instrument Exceptionally well-designed optical pathway with very uniform lighting
Huron TissueScope CF
Low-volume, low-speed, 12 slide fluorescence scanner 6 slide capacity for 2 x 3 inch slides
4 slide capacity for 3x4 inch slides
2 slide capacity for 4x5 inch slides
1 slide capacity for 5x7 inch slides
1 slide capacity for 6x8 inch slides
Two-objective design with magnifications of 20x and 40x 0.25 micron pixels at 40x 0.50 micron pixels at 20x
300+ second scan time at 20x (15mm*15mm) 300+ second scan time at 40x (15mm*15mm) Advanced Fluorescence capability No Z-stacking capability Requires external PC to drive instrument Exceptionally well-designed optical pathway with very uniform lighting
Huron TissueScope LE120
Intermediate-volume, low-speed, 120 slide scanner 60 slide capacity for 2 x 3 inch slides
40 slide capacity for 3x4 inch slides
20 slide capacity for 4x5 inch slides
10 slide capacity for 5x7 inch slides
10 slide capacity for 6x8 inch slides
Two-objective design with magnifications of 20x and 40x 0.25 micron pixels at 40x 0.50 micron pixels at 20x
300+ second scan time at 20x (15mm*15mm) 300+ second scan time at 40x (15mm*15mm) No Fluorescence capability No Z-stacking capability Does not requires external PC to drive instrument – has integrated touchscreen controller Exceptionally well-designed optical pathway with very uniform lighting
Leica Aperio CS2
Low-volume, low-speed, 5-slide scanner 1 slide capacity when loading 2x3 slides
One-objective design with magnifications of 20x (plus a 2x optical changer to yield 40x) 0.25 micron pixels at 40x 0.50 micron pixels at 20x
1x3 inch and 2x3 inch slide capability 100 second scan time at 20x (15mm*15mm) 300 second scan time at 40x (15mm*15mm) No Fluorescence capability Local Z-stacking capability Requires external PC to drive instrument Numerical aperture of light condenser pathway is suboptimal Extensive companion FDA-cleared diagnostic software available
Leica Aperio FL
Low-volume, low-speed, 5-slide fluorescence scanner 1 slide capacity when loading 2x3 slides
One-objective design with magnifications of 20x (plus a 2x optical changer to yield 40x) 0.25 micron pixels at 40x 0.50 micron pixels at 20x
1x3 inch and 2x3 inch slide capability 100 second scan time at 20x (15mm*15mm) 300 second scan time at 40x (15mm*15mm) Integrated Fluorescence capability Local Z-stacking capability Requires external PC to drive instrument Numerical aperture of light condenser pathway is suboptimal Extensive companion FDA-cleared diagnostic software available
Leica Aperio AT2
High-volume, intermediate-speed, 400 slide scanner 1 slide capacity when loading 2x3 slides
One-objective design with magnifications of 20x (plus a 2x optical changer to yield 40x) 0.25 micron pixels at 40x 0.50 micron pixels at 20x
1x3 inch and 2x3 inch slide capability 60 second scan time at 20x (15mm*15mm) 155 second scan time at 40x (15mm*15mm) No Fluorescence capability Local Z-stacking capability Requires external PC to drive instrument Numerical aperture of light condenser pathway is suboptimal Extensive companion FDA-cleared diagnostic software available
Leica Aperio LV1
Specialized Device: Essentially a Robotically Driven Microscope in a box. Control of slides in the X,Y, and Z planes 4 slide capacity Ideal for digital frozen section review and real-time consultation in low-volume settings
Slide available for interactive review in 15 seconds from time of loading Up to 16 concurrent users Low volume whole slide scanning capability Three-objective design with magnifications of:
1.25x, 5x and 20x (with image doubler)
No Fluorescence capability Local Z-stacking capability Requires external PC to drive instrument
MicroScan SL5
Low-volume, intermediate-speed, 1 or 2 slide scanner One-objective design with user-selectable magnifications
2x: 4.54 micron pixels 4x: 2.27 micron pixels 10x: 0.908 micron pixels 20x: 0.454 micron pixels 40x: 0.227 micron pixels
45 second scan time at 20x (15mm*15mm) 169 second scan time at 40x (15mm*15mm) No Fluorescence capability No Z-stacking capability Requires external PC to drive instrument Early versions exhibited optical scan artifacts in the digital images
Now corrected
Motic EasyScan
Low-volume, low-speed, 1 or 6 slide scanner
One-objective design, making use of a high numerical aperture 20x lens 20x: 0.52 micron pixels
40x: 0.26 micron pixels
180 second scan time at 20x (15mm*15mm)
360 second scan time at 40x (15mm*15mm)
No Fluorescence capability
True Z-stacking capability
Requires external PC to drive instrument
Motic EasyScanPro
Low-volume, intermediate-speed, 1 or 6 slide scanner
One-objective design, making use of an ultra-high numerical aperture 20x lens 20x: <0.52 micron pixels
40x: <0.26 micron pixels
90 second scan time at 20x (15mm*15mm)
180 second scan time at 40x (15mm*15mm)
No Fluorescence capability
True Z-stacking capability
Requires external PC to drive instrument
Objective Imaging Glissando
Low-volume, intermediate-speed, 1 or 2 slide scanner 1 slide capacity when loading 2x3 slides
One-objective design, making use of a magnification doubler 20x: 0.50 micron pixels 40x: 0.275 micron pixels
35 second scan time at 20x (15mm*15mm) 140 second scan time at 40x (15mm*15mm) No Fluorescence capability True Z-stacking capability Requires external PC to drive instrument
Philips UFS
High-volume, high-speed, 300 slide scanner One-objective design with magnifications of 40x
0.25 micron pixels at 40x
Random access system for each slide basket 1x3 inch slide capability only 35 second scan time at 20x (15mm*15mm) 60 second scan time at 40x (15mm*15mm) No Fluorescence capability No Z-stacking capability in current model(planned for next model) Does not requires external PC to drive instrument– has integrated touchscreen
and controller Part of overall FDA-cleared “pixel pipeline” for primary histopathological
diagnosis
Roche Ventana iScan Coreo
High-volume, low-speed, 160 slide scanner Multi-objective design with magnifications of:
4x: 2.27 micron pixels 10x: 0.908 micron pixels 20x: 0.454 micron pixels 40x: 0.227 micron pixels
1x3 inch slide capability only 120 second scan time at 20x (15mm*15mm) 450 second scan time at 40x (15mm*15mm) No Fluorescence capability Local Z-stacking capability Does not require external PC to drive instrument – has integrated touchscreen and
controller Extensive companion FDA-cleared diagnostic software available
Roche Ventana iScan HT
High-volume, high-speed, 360 slide scanner Multi-objective design with magnifications of:
4x: 2.27 micron pixels 10x: 0.908 micron pixels 20x: 0.454 micron pixels 40x: 0.227 micron pixels
1x3 inch slide capability only 45 second scan time at 20x (15mm*15mm) 72 second scan time at 40x (15mm*15mm) No Fluorescence capability Local Z-stacking capability Does not require external PC to drive instrument – has integrated touchscreen and
controller Extensive companion FDA-cleared diagnostic software available
Sakura VisionTek
Low-volume, low-speed, 4 slide scanner Three-objective design with magnifications of:
2.5x: 2.2 micron pixels
10x: 0.55 micron pixels 20x: 0.275 micron pixels
1x3 inch slide capability only 175 second scan time at 20x (15mm*15mm) >400 second scan time at 40x (15mm*15mm) No Fluorescence capability True Z-stacking capability Requires external PC to drive instrument
Sakura VisionTek M6
Low-volume, intermediate-speed, 4 slide scanner Three-objective design (Carl Zeiss) with magnifications of:
2.5x: 2.2 micron pixels
20x: 0.275 micron pixels 40x: 0.138 micron pixels
1x3 inch slide capability only 90 second scan time at 20x (15mm*15mm) 360 second scan time at 40x (15mm*15mm) No Fluorescence capability True Z-stacking capability Requires external PC to drive instrument
Grundium Ocus
Low-volume, single scanner
Single-objective design (proprietary), based on a ground-up redesign of optics obtained from experience in the design of smart phone high-performance cameras
with magnifications of: 20x: 0.48 micron pixels or
40x: 0.24 micron pixels
1x3 inch slide capability only
120 second scan time at 20x (15mm*15mm)
No Fluorescence capability
True Z-stacking capability
No external PC required to drive instrument – Smart phone interface-capable
Grundium Ocus
Extremely compact, owing to miniaturization technologies developed in the smart phone industry
Potential for portable stand-alone operation with WiFi connectivity, owing to battery operation
Fully roboticized stage and focus Auto-focus Integrated Web Server technology yielding
capability for stand-alone operation without the use of an image-server
Potential for effective utilization in low resource settings
Strategic Considerations
You have the greatest leverage to secure the best possible purchase terms prior to signing the final contract
On premises vs. cloud-based storage Digital mediate retention policy (how long to keep vs. delete) Case cohort sizes for pre-activation validation Site assessment
Network bandwidth
Local health system and departmental IT support
Storage Costs
Data format and data ownership
Given a single slide’s typical 1 x 1 cm2 scanning area(or 3.7 cm2 if we’re being honest)
05
• (1k - 2k) *300 MB = 300-600 Gb per day
• 9 - 18 Tb per month
• 108 - 144 TB per year (for 1 x 1 cm slides)
• 1.479-1.971 PB per year (for actual 3.7 cm2 slide areas)
Actual Production Storage Required
041000 - 2000 slides/day from a typical practice causes upwards scaling of storage requirements
Scaling Up
03Reduced to ~300 MB
LosslessCompression
0240k x 40k = 1.6 GB (single channel) or4.8 GB (RGB), prior to lossless compression
1 cm2 patch
1 cm x 10 mm/1 cm x 1000 microns/1 mm x 4 pixels/micron =
40,000 pixels/cm
01Slide Linear Density
Typical Cloud Storage Pricing Calculation
Service (1 x 1 cm) Monthly Fee
30 TB of Multi-Regional Storage 399.36
6 TB Network Traffic (6,050GB) at $0.11/per GB 675.77
Network Ingress 0.00
$0.05/per 10,000 PUT/POST/GET bucket/GET service requests: $1.00 1.00
$0.004/per 10,000 GET object and HEAD requests: $10.00 10.00
Total per month 1,086.13
Total per year 13,033.56
Service (2.5 x 2.5 cm) Monthly Fee
60 TB of Multi-Regional Storage 1,597.44
9TB Network Traffic (9,216GB) at $0.11/per GB 1,013.76
Network Ingress 0.00
$0.05/per 10,000 PUT/POST/GET bucket/GET service requests: $1.00 1.00
$0.004/per 10,000 GET object and HEAD requests: $10.00 10.00
Total per month 2,622.20
Total per year 31,466.40
Assuming 80,000 cases per year (@ 10 slides/case)….$0.016 per slide for storage and networking
$0.039 per slide for storage and networking
Data Format and Data Ownership
Ideally, the pathology department will have unfettered access to the NATIVE pixels/data that their WSI systems generate (accessed to compressed data extraction is not sufficient) Ideally, full DICOM support is provided (or at least promised by a certain date)
Some vendors utilize an internal proprietary format. This is fine, so long as there is a clear and efficient pathway by which native data can be extracted quickly and efficiently (e.g. 30 minutes per conversion is not acceptable)
Vendors must provide an API to their systems for controlling worklists, workflow and data extraction; this will allow for the possible integration with local AP-LIS solutions
All of these above issues can be stipulated in the initial Tender that is distributed to potential vendors
The goal is to foster the creation of an open data ecosystem, where no one vendor has a potential blocking position, by virtue of proprietary formats, interfaces and policies.
Closing Thoughts
Generate a comprehensive set of use-cases and requirements for each workflow, prior to acquiring any hardware
Attempt, whenever possible, to engineer “device refresh” terms into purchase or lease contracts
Be cautious of single-vendor solutions, as a diverse ecosystem can confer “hybrid vigor” to the overall continuity of service
Be vigilant of the emergence of practice guidelines that will inform rational data retention strategies, given the large associated storage requirements for WSI workflow