From the conventional microscope to the digital slide scanner in routine diagnostic histopathology Sten Thorstenson Medical director, MD Department of Pathology and Cytology Kalmar County Hospital Kalmar, Sweden
Start of Kalmar´s digital journey • In 1999 we started our digital telepathology service of frozen sections to Västervik (150 km north of Kalmar). Pathsight system. • The trimming, sectioning and staining was performed by technicians in the Dept. of clinical chemistry, Västervik. • Images (and sound) were transferred via 6 ISDN lines. Primary usage: parathyroid and sentinel node diagnostics. • In January of 2008 Pathsight was replaced by a small Scanscope scanner and images are nowdays transferred in the county intranetwork. • Today we have >10 years experience of digital frozen section telepathology service.
Why did Kalmar continue beyond the digital telepathology frozen sections? • When one of our collegues got acute problems from his cervical spine we started to investigate different possibilities to minimize the working hours in the microscope. • Could the digital technique be a possible solution?
Kalmar´s main reasons for digitalisation • Improved ergonomics. • Networking with other pathology laboratories.
Advantages • Networking with labs having the capacity and the top notch knowledge. Possibility to redistribute diagnostic material. • Possibility to work from home. • Consultations are easily made. • Clinico-pathological conferences without glass slides. • Measurements are easy using the built in ruler. • Image analysis (prognostics, prediction). • Easier to recruit young pathologists.
Problems • The data volumes become ”enormous”. The Kalmar lab initially estimated 36000 Gb/year (-06: 16781 histopathology reports, 59412 slides, 0,6 Gb/slide during the validation). • Only 1 focal plane, i e it is not possible to focus through the specimen. • Our initial tests showed that scanning at 200X and a compression quality of 70 resulted in an average scan time/slide of 5 minutes (using slides not optimized for scanning). • Scanning at 200X gives a limiting resolution regarding high power diagnostics. Scanning at 400X results in 3 times as long scan time as well as larger data files. • The precision of the lab has to be improved.
The process • Testning of 3 different scanners (2007). • Installation of hardware, software and network. Laboratory adjustments etc. (February 2008). • The validation process (4/3 – 27/9 2008). • Up and fully running (October 2008).
Our choice of hard- and software • Scanners: 2 Aperio Scanscope XT (local agent LRI, Sweden) • Image database: Picsara (Euromed Networks, Sweden). • LIS: SymPathy (Tieto, Sweden). • Workstations: 7 Dell Precision 3400 (4 Gb RAM and Nvidia Quadro FX 3700 with 512 RAM). • Each workstation has 2 LCD monitors (Dell 20” and 30”).
Necessary adjustments • Transition to 2D datamatrix barcodes on the slide labels. • Integration of LIS with image database. • Trimming/grossing: cut smaller specimens! • Clean slides, thin and non-wrinkled sections, fewer sections/slide, positioning of the sections on the slides, staining quality, coverslip precision, drying of the slides (60°C, 1 hr) before scanning etc. • Logistics within the lab: for example, our secretaries manage the scanning (including the manual rescans). • The pathologist: it takes some time to trust the image on the monitor. What is difficult to diagnose on the monitor is probably just as difficult in the microscope!
The validation process • Duration: 6,5 months. 3 specialists and 1 resident. • 1 colleague in Karlskrona (80 km south of Kalmar) for consultations via the national hospital network (10 Mbit). • Each specimen was primarily diagnosed on the monitor and immediately thereafter in the microscope. Each specimen was documented in a protocol. • The validation did not only concern the diagnostic correctness but also changes of the laboratory routines, logistics, servers, network, interfaces, firewalls as well as calculation of the required data storage volume.
Experiences from the validation • 14.326 slides (of most topographies och procedural types) were scanned at 200X magnification using compression quality 70. Time required: 5 minutes/slide. • 24 hr scanning worked very well. All slides (with few exceptions) were mechanically transported OK in the scanner. • Very few problems relating to the scanner, which was automatically restarted each morning before work. • 2 web cameras were installed in the scanner connected to LRI to help rapid support. • At automatic scanning 2% of the slides were refused by the scanner (2 slides of 100 needed a manual rescan) using the parameter setting ”coverslip”.
Experiences from the validation • The scanners should be hooked up to an UPS. • The scanners should be cleaned (and greased) at least every 6 months. • The halogen light bulbs should be replaced at least every second month. The light intensity decreases continously resulting in the need of recalibrating the camera. • We would like to see another type of bulb with a constant intensity until the bulb is wasted.
Experiences from the validation • 606 cases (2480 slides) were diagnostically validated. In 2 cases (0,3%) the diagnoses were changed after conventional microscopy (1 missed fungus, 1 missed Helicobacter) – both cases were high power diagnostics. • Scanning at 200X magnification is insufficient for counting mitoses and any other high power diagnostics. • In those cases we use the microscope or ask for a rescan at 400X magnification. • Image transfer via the national hospital network (10Mbit) worked OK.
Experiences from the validation • Our subjective opinion: in many cases the digital diagnostics is superior (e g the overview, measurements, comparing ”slides”). • >75% of all histopathology can be diagnosed on the monitor. • Compared to conventional microscopy, where the position of the head is quite fixed, using the monitor for diagnostics has definitely improved the ergonomics.
The modern pathologist´s cockpit Imagescopeinterface Picsara interface SymPathy interface (Old fashioned microscope)
Clearly improved ergonomics! Coffee! The modernpathologist Anyone wants to work as a pathologist in Kalmar ? Phone +46 480 448019.
Data storage • After adjustments of the trimming of specimens and the lab procedures the average data size of a slide has decreased from 0,6 Gb to 0,4 Gb. • The Kalmar lab today would need 24 000 Gb/year (excluding cytology) for image storage. • Our primary incentive to diagnose virtual slides was to achieve improved ergonomics. • Consequently the images can be deleted after the reports are finished (including eventual consultations, clinico-pathological conferences etc). Cut off is set to 6 months. • 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).
Are we allowed to delete virtual slides being the basis for reports? • The image is an exact working copy of the slide. • The original slides are always delivered to the pathologist, so he/she can choose whether to use the old fashion microscope or the digital images. • Therefore the images can be deleted when the case is closed. The original biologic material (blocks and slides), however, is filed permanently. This is valid for Sweden.
Kalmar today • >60000 histopathology slides have been scanned. • 24 hr scanning. • 1,5 years experience of routine histopathology diagnostics. • >75% of the routine histopathology is diagnozed digitally. • 10 years experience of digital telepathology frozen section service. • Some clinico-pathological conferences digitally. • Individual digital slide conferencing (on demand from clinicians).
Continued development • Applying semiautomatic or automatic techniques for measurements, e g percentage cellular distribution, nuclear area/dysplasia etc. More objective pathology. • Image analysis (prediction, e g ER/PGR, HER-2, Ki-67 index). Expensive diagnostics and treatment. More reproducible prediction. • Improvements of the interfaces, HID etc. Voice recognition? • Scanning at multiple focal planes as a standard to allow ”focusing” through a section. • Faster scanning at 400X magnification to allow more liberal direct usage of high power diagnostics. Preferably all slides.
Continued development • Scanning of large sections, >2x normal slide size (e g prostatectomies, breast cancers, rectal carcinomas, Whipple specimens) • Digitalisation of the cytology using the liquid based cytology technique (scan area of 10 mm diameter with cells in a monolayer results in a reasonable scan time and relatively small data volumes compared to scanning of whole slides).Scanning at 400X.
So ………. • The future is here. • The digital platform is ready, validated and in full usage in the clinical situation. • LET´S ENTER THE NEW ERA OF DIGITAL HISTOPATHOLOGY!! • Sten.Thorstenson@LtKalmar.se THANK YOU
KALMAR?? Kalmar: 62.000 inhabitants Kalmar county: 235.000 inhabitants and 3 hospitals Pathology departments: 1 Distances: Stockholm 310 km (192 mi) Latvia 290 km (180 mi) Copenhagen 260 km (162 mi) Berlin 500 km (312 mi) San Diego 9150 km (5685 mi)