From the conventional From the conventional microscope to the digital slide microscope to the digital slide scanner in routine diagnostic scanner in routine diagnostic

histopathologyhistopathology

Sten ThorstensonSten ThorstensonMedical director, MDMedical director, MD

Department of Pathology and CytologyDepartment of Pathology and CytologyKalmar County HospitalKalmar County Hospital

Kalmar, SwedenKalmar, Sweden

Start of Kalmar´s digital journeyStart of Kalmar´s digital journey • In 1999 we started our digital telepathology service of In 1999 we started our digital telepathology service of

frozen sections to Västervik (150 km north of Kalmar). frozen sections to Västervik (150 km north of Kalmar). Pathsight system.Pathsight system.

• The trimming, sectioning and staining was performed by The trimming, sectioning and staining was performed by technicians in the Dept. of clinical chemistry, Västervik.technicians in the Dept. of clinical chemistry, Västervik.

• Images (and sound) were transferred via 6 ISDN lines. Images (and sound) were transferred via 6 ISDN lines. Primary usage: parathyroid and sentinel node Primary usage: parathyroid and sentinel node diagnostics.diagnostics.

• In January of 2008 Pathsight was replaced by a small In January of 2008 Pathsight was replaced by a small Scanscope scanner and images are nowdays Scanscope scanner and images are nowdays transferred in the county intranetwork.transferred in the county intranetwork.

• Today we have >10 years experience of digital frozen Today we have >10 years experience of digital frozen section telepathology service.section telepathology service.

Why did Kalmar continue beyond Why did Kalmar continue beyond the digital telepathology frozen the digital telepathology frozen

sections? sections?

• When one of our collegues got acute When one of our collegues got acute problems from his cervical spine we problems from his cervical spine we started to investigate different possibilities started to investigate different possibilities to minimize the working hours in the to minimize the working hours in the microscope.microscope.

• Could the digital technique be a possible Could the digital technique be a possible solution?solution?

Kalmar´s main reasons for Kalmar´s main reasons for digitalisationdigitalisation

• Improved ergonomics.Improved ergonomics.

• Networking with other pathology Networking with other pathology laboratories.laboratories.

AdvantagesAdvantages

• Networking with labs having the capacity and the Networking with labs having the capacity and the top notch knowledge. Possibility to redistribute top notch knowledge. Possibility to redistribute diagnostic material.diagnostic material.

• Possibility to work from home.Possibility to work from home.• Consultations are easily made.Consultations are easily made.• Clinico-pathological conferences without glass Clinico-pathological conferences without glass

slides.slides.• Measurements are easy using the built in ruler.Measurements are easy using the built in ruler.• Image analysis (prognostics, prediction).Image analysis (prognostics, prediction).• Easier to recruit young pathologists.Easier to recruit young pathologists.

ProblemsProblems

• The data volumesThe data volumes become ”enormous”. The Kalmar lab become ”enormous”. The Kalmar lab initially estimated initially estimated 36000 Gb/year36000 Gb/year (-06: 16781 (-06: 16781 histopathology reports, 59412 slides, 0,6 Gb/slide during histopathology reports, 59412 slides, 0,6 Gb/slide during the validation).the validation).

• Only Only 1 focal plane1 focal plane, i e it is not possible to focus through , i e it is not possible to focus through the specimen. the specimen.

• Our initial tests showed that scanning at 200X and a Our initial tests showed that scanning at 200X and a compression quality of 70 resulted in an average compression quality of 70 resulted in an average scan scan time/slidetime/slide of 5 minutes (using slides not optimized for of 5 minutes (using slides not optimized for scanning).scanning).

• Scanning at 200X gives a limiting Scanning at 200X gives a limiting resolutionresolution regarding regarding high power diagnostics. Scanning at 400X results in 3 high power diagnostics. Scanning at 400X results in 3 times as long scan time as well as larger data files.times as long scan time as well as larger data files.

• The The precisionprecision of the lab has to be improved. of the lab has to be improved.

The processThe process

• Testning of 3 different scanners (2007).Testning of 3 different scanners (2007).

• Installation of hardware, software and Installation of hardware, software and network. Laboratory adjustments etc. network. Laboratory adjustments etc. (February 2008).(February 2008).

• The validation process (4/3 – 27/9 2008).The validation process (4/3 – 27/9 2008).

• Up and fully running (October 2008).Up and fully running (October 2008).

Our choice of hard- and softwareOur choice of hard- and software

• Scanners: 2 Aperio Scanscope XT (local agent Scanners: 2 Aperio Scanscope XT (local agent LRI, Sweden)LRI, Sweden)

• Image database: Picsara (Euromed Networks, Image database: Picsara (Euromed Networks, Sweden). Sweden).

• LIS: SymPathy (Tieto, Sweden). LIS: SymPathy (Tieto, Sweden). • Workstations: 7 Dell Precision 3400 (4 Gb RAM Workstations: 7 Dell Precision 3400 (4 Gb RAM

and Nvidia Quadro FX 3700 with 512 RAM).and Nvidia Quadro FX 3700 with 512 RAM).• Each workstation has 2 LCD monitors (Dell 20” Each workstation has 2 LCD monitors (Dell 20”

and 30”).and 30”).

Necessary adjustmentsNecessary adjustments

• Transition to 2D datamatrix barcodes on the slide labels.Transition to 2D datamatrix barcodes on the slide labels.• Integration of LIS with image database.Integration of LIS with image database.• Trimming/grossing: cut smaller specimens!Trimming/grossing: cut smaller specimens!• Clean slides, thin and non-wrinkled sections, fewer Clean slides, thin and non-wrinkled sections, fewer

sections/slide, positioning of the sections on the slides, sections/slide, positioning of the sections on the slides, staining quality, coverslip precision, drying of the slides staining quality, coverslip precision, drying of the slides (60(60°C, 1 hr)°C, 1 hr) before scanning etc. before scanning etc.

• Logistics within the lab: for example, our secretaries Logistics within the lab: for example, our secretaries manage the scanning (including the manual rescans).manage the scanning (including the manual rescans).

• The pathologist: it takes some time to trust the image on The pathologist: it takes some time to trust the image on the monitor. What is difficult to diagnose on the monitor the monitor. What is difficult to diagnose on the monitor is probably just as difficult in the microscope!is probably just as difficult in the microscope!

The validation process

• Duration: 6,5 months. 3 specialists and 1 resident.Duration: 6,5 months. 3 specialists and 1 resident.• 1 colleague in Karlskrona (80 km south of Kalmar) for 1 colleague in Karlskrona (80 km south of Kalmar) for

consultations via the national hospital network (10 Mbit).consultations via the national hospital network (10 Mbit).• Each specimen was primarily diagnosed on the monitor Each specimen was primarily diagnosed on the monitor

and immediately thereafter in the microscope. Each and immediately thereafter in the microscope. Each specimen was documented in a protocol.specimen was documented in a protocol.

• The validation did not only concern the diagnostic The validation did not only concern the diagnostic correctness but also changes of the laboratory routines, correctness but also changes of the laboratory routines, logistics, servers, network, interfaces, firewalls as well as logistics, servers, network, interfaces, firewalls as well as calculation of the required data storage volume.calculation of the required data storage volume.

Experiences from the validationExperiences from the validation

• 14.326 slides (of most topographies och procedural 14.326 slides (of most topographies och procedural types) were scanned at 200X magnification using types) were scanned at 200X magnification using compression quality 70. Time required: 5 minutes/slide.compression quality 70. Time required: 5 minutes/slide.

• 24 hr scanning worked very well. All slides (with few 24 hr scanning worked very well. All slides (with few exceptions) were mechanically transported OK in the exceptions) were mechanically transported OK in the scanner.scanner.

• Very few problems relating to the scanner, which was Very few problems relating to the scanner, which was automatically restarted each morning before work. automatically restarted each morning before work.

• 2 web cameras were installed in the scanner connected 2 web cameras were installed in the scanner connected to LRI to help rapid support.to LRI to help rapid support.

• At automatic scanning 2% of the slides were refused by At automatic scanning 2% of the slides were refused by the scanner (2 slides of 100 needed a manual rescan) the scanner (2 slides of 100 needed a manual rescan) using the parameter setting ”coverslip”. using the parameter setting ”coverslip”.

Experiences from the validationExperiences from the validation

• The scanners should be hooked up to an UPS.The scanners should be hooked up to an UPS.• The scanners should be cleaned (and greased) The scanners should be cleaned (and greased)

at least every 6 months.at least every 6 months.• The halogen light bulbs should be replaced at The halogen light bulbs should be replaced at

least every second month. The light intensity least every second month. The light intensity decreases continously resulting in the need of decreases continously resulting in the need of recalibrating the camera. recalibrating the camera.

• We would like to see another type of bulb with a We would like to see another type of bulb with a constant intensity until the bulb is wasted.constant intensity until the bulb is wasted.

Experiences from the validationExperiences from the validation

• 606 cases (2480 slides) were diagnostically 606 cases (2480 slides) were diagnostically validated. In 2 cases (0,3%) the diagnoses were validated. In 2 cases (0,3%) the diagnoses were changed after conventional microscopy (1 changed after conventional microscopy (1 missed fungus, 1 missed Helicobacter) – both missed fungus, 1 missed Helicobacter) – both cases were high power diagnostics.cases were high power diagnostics.

• Scanning at 200X magnification is insufficient for Scanning at 200X magnification is insufficient for counting mitoses and any other high power counting mitoses and any other high power diagnostics.diagnostics.

• In those cases we use the microscope or ask for In those cases we use the microscope or ask for a rescan at 400X magnification.a rescan at 400X magnification.

• Image transfer via the national hospital network Image transfer via the national hospital network (10Mbit) worked OK.(10Mbit) worked OK.

Experiences from the validationExperiences from the validation

• Our subjective opinion: in many cases the digital Our subjective opinion: in many cases the digital diagnostics is superior (e g the overview, diagnostics is superior (e g the overview, measurements, comparing ”slides”).measurements, comparing ”slides”).

• >75% of all histopathology can be diagnosed on >75% of all histopathology can be diagnosed on the monitor.the monitor.

• Compared to conventional microscopy, where Compared to conventional microscopy, where the position of the head is quite fixed, using the the position of the head is quite fixed, using the monitor for diagnostics has definitely improved monitor for diagnostics has definitely improved the ergonomics.the ergonomics.

The modern pathologist´s cockpit

Picsara interfaceImagescope interface

SymPathy interface

(Old fashioned microscope)

Clearly improved ergonomics!

The modern pathologist

Coffee!Coffee!

Anyone wants to work as a pathologist in Kalmar ? Phone +46 480 448019.

Data storageData storage• After adjustments of the trimming of specimens and the lab After adjustments of the trimming of specimens and the lab

procedures the average data size of a slide has decreased from 0,6 procedures the average data size of a slide has decreased from 0,6 Gb to 0,4 Gb.Gb to 0,4 Gb.

• The Kalmar lab today would need 24 000 Gb/year (excluding The Kalmar lab today would need 24 000 Gb/year (excluding cytology) for image storage.cytology) for image storage.

• Our primary incentive to diagnose virtual slides was to achieve Our primary incentive to diagnose virtual slides was to achieve improved ergonomicsimproved ergonomics..

• Consequently the images can be deleted after the reports are Consequently the images can be deleted after the reports are finished (including eventual consultations, clinico-pathological finished (including eventual consultations, clinico-pathological conferences etc). Cut off is set to 6 months. conferences etc). Cut off is set to 6 months.

• 12 000 Gb is what we have today as a constant storage volume. 12 000 Gb is what we have today as a constant storage volume. • A script is run automatically to dump images. FIFO (first in first out).A script is run automatically to dump images. FIFO (first in first out).

Are we allowed to delete virtual Are we allowed to delete virtual slides being the basis for reports?slides being the basis for reports?

• The image is an exact working copy of the slide.The image is an exact working copy of the slide.• The original slides are The original slides are alwaysalways delivered to the delivered to the

pathologist, so he/she can choose whether to pathologist, so he/she can choose whether to use the old fashion microscope or the digital use the old fashion microscope or the digital images.images.

• Therefore the images can be deleted when the Therefore the images can be deleted when the case is closed. The original biologic material case is closed. The original biologic material (blocks and slides), however, is filed (blocks and slides), however, is filed permanently. This is valid for Sweden.permanently. This is valid for Sweden.

Kalmar todayKalmar today

• >60000 histopathology slides have been scanned.>60000 histopathology slides have been scanned.• 24 hr scanning.24 hr scanning.• 1,5 years experience of routine histopathology 1,5 years experience of routine histopathology

diagnostics.diagnostics.• >75% of the routine histopathology is diagnozed digitally.>75% of the routine histopathology is diagnozed digitally.• 10 years experience of digital telepathology frozen 10 years experience of digital telepathology frozen

section service.section service.• Some clinico-pathological conferences digitally.Some clinico-pathological conferences digitally.• Individual digital slide conferencing (on demand from Individual digital slide conferencing (on demand from

clinicians).clinicians).

Continued development Continued development

• Applying semiautomatic or automatic techniques for Applying semiautomatic or automatic techniques for measurements, e g percentage cellular distribution, measurements, e g percentage cellular distribution, nuclear area/dysplasia etc. nuclear area/dysplasia etc. More objective pathologyMore objective pathology..

• Image analysis (prediction, e g ER/PGR, HER-2, Ki-67 Image analysis (prediction, e g ER/PGR, HER-2, Ki-67 index). Expensive diagnostics and treatment. index). Expensive diagnostics and treatment. More More reproducible predictionreproducible prediction..

• Improvements of the Improvements of the interfacesinterfaces, , HIDHID etc. Voice etc. Voice recognition?recognition?

• Scanning at multiple focal planes as a standard to allow Scanning at multiple focal planes as a standard to allow ”focusing” through a section”focusing” through a section..

• Faster scanning at 400X magnification to allow more Faster scanning at 400X magnification to allow more liberal direct usage of high power diagnostics. Preferably liberal direct usage of high power diagnostics. Preferably all slides.all slides.

Continued development Continued development

• Scanning of large sections, >2x normal slide Scanning of large sections, >2x normal slide size (e g prostatectomies, breast cancers, rectal size (e g prostatectomies, breast cancers, rectal carcinomas, Whipple specimens) carcinomas, Whipple specimens)

• Digitalisation of the Digitalisation of the cytologycytology using the liquid using the liquid based cytology technique (scan area of 10 mm based cytology technique (scan area of 10 mm diameter with cells in a monolayer results in a diameter with cells in a monolayer results in a reasonable scan time and relatively small data reasonable scan time and relatively small data volumes compared to scanning of whole slides).volumes compared to scanning of whole slides).Scanning at 400X.Scanning at 400X.

So ……….So ……….

• The future is here.The future is here.• The digital platform is ready, validated and in full The digital platform is ready, validated and in full

usage in the clinical situation.usage in the clinical situation.

• LET´S ENTER THE NEW ERA OF DIGITAL LET´S ENTER THE NEW ERA OF DIGITAL HISTOPATHOLOGY!!HISTOPATHOLOGY!!

• Sten.Thorstenson@LtKalmar.seSten.Thorstenson@LtKalmar.se

THANK YOUTHANK YOU

KALMAR??KALMAR??

Kalmar: 62.000 inhabitantsKalmar: 62.000 inhabitants

Kalmar county: 235.000 inhabitants Kalmar county: 235.000 inhabitants and 3 hospitalsand 3 hospitals

Pathology departments: 1Pathology departments: 1

Distances: Distances: Stockholm 310 km (192 mi)Stockholm 310 km (192 mi)

Latvia 290 km (180 mi)Latvia 290 km (180 mi)

Copenhagen 260 km (162 mi)Copenhagen 260 km (162 mi)

Berlin 500 km (312 mi)Berlin 500 km (312 mi)

San Diego 9150 km (5685 mi)San Diego 9150 km (5685 mi)