Telepathology and Distant Diagnosis

with SMALL SIZE VIRTUAL SLIDES

(SSVS)
Eng. Marcano, Fco & Prof. Dr. O. Ferrer-Roca 2007.

UNESCO Chair in Telemedicine

University of La Laguna

Quality Control in Telemedicine - Biobanking

CATAI - XVI Winter Course
ULL - XXI Image Analisys Course

http://www.teide.net/catai
 Contents
• Introduction
• VS
• SSVS
• SSVS quality assessment
• Results
• Conclusions
 Virtual Slides
• Specimens converted to digital
images

• Images are transmitted over

networks, Internet

Bone biopsy
Area: 2.8x8.2 mm
Pixels: about 290M

• Remote Analysis, Diagnosis,

teaching purposes © Telemedicine Research Group - University of Udine, Italy
 Virtual Slide Capture Systems
High power VS (40x) 
Image size in the order of Gigabytes

Expensive equipments
50000€ - 250000€
 Virtual Slides Size
• Demands a
lot of
storage

• JPEG based
images
20x
compression

© Department of Pathology. Clínica Universitaria. University of Navarra. Pamplona. Spain.

 Virtual Slides Size - QC
• Technique:
linear
scanning

• Image
artifacts

• Equipment
price vs.
Image
quality
?

© Department of Pathology. Clínica Universitaria. University of Navarra. Pamplona. Spain.

 Virtual Slides Size - QC
• Good
Alignment

© Department of Pathology. Clínica Universitaria. University of Navarra. Pamplona. Spain.

 VS – High Power
 Not always
necessary
to have
high-power
images

 Images:
several
Gigabytes 1.3X 3.9X

11.1X 40X
 e-Slides
• Telemedicine Research Group - University of Udine, Italy

 Technique:
stitching of
images

 Cheaper
approach

 JPEG based
images
© Telemedicine Research Group - University of Udine, Italy

 Size: still
very large
 e-Slides - QC
 Stitching of
images 

more image
artifacts

© Telemedicine Research Group - University of Udine, Italy

 e-Slides - QC
 Problems
with image
alignment

© Telemedicine Research Group - University of Udine, Italy

 Small Size Virtual Slides –
SSVS©
• Novel Technique

• Generates digital slides small in size

• High resolution cameras (8-12 Mpx)

• Excellent achromatic planapochromatic (infinite)

optics

SSVS© 2008
 Small Size Virtual Slides –
SSVS©
• Uses Image-Compression format: JPEG2000
(ISO 15444-1, Wavelet)

• Take advantage of JPEG2000 Image format to

facilitate:
• navigation,
• zooming,
• transmission,
• storage
SSVS© 2008
 JPEG2000
• Created by the Joint Photographic Experts Group committee
(2000)

• Intended to supersede discrete cosine transform-based JPEG

standard (1991)

• Standard Filename extension:

jp2 (ISO/IEC 15444-1 conforming files)
jpx (Extended part-2 specifications or ISO/IEC 15444-2)

• Included in DICOM sup. 61 (Jan 2002)

 JPEG2000 Standard - Parts
• Part 1, Core coding system (intended as royalty and license-fee free -
NB NOT patent-free)
• Part 2, Extensions (adds more features and sophistication to the core)
• Part 3, Motion JPEG 2000
• Part 4, Conformance
• Part 5, Reference software (Java and C implementations are available)
• Part 6, Compound image file format (document imaging, for pre-press
and fax-like applications, etc.)
• Part 7 has been abandoned
• Part 8, JPSEC (security aspects)
• Part 9, JPIP (interactive protocols and API)
• Part 10, JP3D (volumetric imaging)
• Part 11, JPWL (wireless applications)
• Part 12, ISO Base Media File Format (common with MPEG-4)
 JPEG2000
• Complex algorithm for compression / decompression takes a long time
8 7 8 8 34 34 34 34
7 7 8 8 34 34 34 34
8 8 12 12 34 34 34 34
8 8 12 12 34 34 34 34
34 34 34 34 55 55 55 55
34 34 34 34 55 55 55 55
34 34 34 34 55 55 55 55
34 34 34 34 55 55 55 55

Rate
Control

Source Tier-1 Tier-2 Compressed

Image Color Wavelet Encoder
Tiling Quantization Encoder Image
(Modeling &
Transformation Transform (Stream
Arithmetic
Creation)
Coding)

decompression EBCOT - Embedded Block

Coding with Optimal
Truncation
 JPEG2000
• Higher compression ratios, images get blurred
570k 57k 6k 2k
 JPEG2000
Compression factor: 1:250
Jpeg2000 - blurred Jpeg - blocked
Distant Diagnosis - TEXCAN©-
II
• TEXCAN-II® implements SSVS technique,
allowing:

• Zoom-Focus©
• Spatial resolution  extreme digital zoom;
• High quality focused image
• Small size of compressed images
• Fast & efficient distant consultation
• Non-expensive digital virtual microscope
 TEXCAN®-II Capture System

CCD Camera 8Mpixels,

firewire 1394.a

4x – 0.13 NA
20x – 0.46 NA (ROI’s)

Intel 3.4 GHz Pentium® 4 /

Intel® Core™2 Duo,
4 Gb RAM
 TEXCAN®-II Assessment
Tools
Preparación Diagnóstico conocido Maligno Inflamación F.S.M.*
CITOLOGIA ORINA: Positivo para celulas
malignas. Sugestivo de Carcinoma de
1 celulas claras
CITOLOGÍA ORINA: Citologia positiva
para celulas tumorales malignas. Frotis
+
www.cataibreezee.ull.es:81.
2 sugestivo de Carcinoma. +
CITOLOGÍA DE LÍQUIDO PLEURAL.
CITOLOGÍA SOSPECHOSA DE
MALIGNIDAD. FROTIS CON INTENSA
3 LINFOCITOSIS. + +
CITOLOGÍA DE LÍQUIDO PLEURAL:
CITOLOGÍA POSITIVA PARA CÉLULAS
TUMORALES MALIGNAS. Frotis sugestivo
4 de Carcinoma. +
PUNCIÓN ASPIRACIÓN DE MAMA: Frotis
sugestivos de mastopatía fibroquística
con lesión epitelial proliferativa benigna
Samples 5 intraquística.

Stat. Software
CITOLOGÍA DE LAVADO PERITONEAL:
CITOLOGÍA POSITIVA PARA CÉLULAS
TUMORALES MALIGNAS. Frotis sugestivo
6 de Carcinoma +
CITOLOGÍA DE LÍQUIDO PLEURAL:
CITOLOGÍA SOSPECHOSA DE
7 MALIGNIDAD. + +

Frotis con estimulo estrogenico mediano,

algo inflamatorio, con espermatozoides,
elementos cervicales asi como cambios
celulares queratosicos y celulas
pavimentosas con atipias nucleares
moderadas. HSIL (High grade squamous
8 intraepitelial lesion) + + +
Frotis pseudoluteal, algo inflamatorio,
con elementos endocervicales sin
anomalias. Hay cambios celulares
queratosicos, asi como binucleaciones y
elementos pavimentosos con atipias
nucleares. LSIL-HPV? (Lesion escamosa
intraepitelial de bajo grado-Human
9 Papiloma Virus?) + +
Frotis mixto, moderadamente
inflamatorio, con alteraciones celulares
degenerativas, asi como escasos
elementos pavimentosos con atipias
10 ligeras, de probable origen reactivo. +
Estimulo estrogenico moderado, con
citolisis, algo inflamatorio. Elementos
cervicales bien conservados y escasos
elementos pavimentosos con atipias
ligeras. ASCUS (Atipical scamous cells of
11 unknown significance). +
Estimulo estrogenico moderado, con
citolisis, algo inflamatorio. Elementos JPIP
cervicales bien conservados y celulas
metaplasicas con atipias nucleares y
algun pseudokoilocito, asi como cambios
JPEG2000
queratosicos. LSIL-HPV (Lesion escamosa
intraepitelial de bajo grado-Human
12 Papiloma Virus) +
13 Microcarcinoma papilar de tiroides. +
14 Adenoma tubular
15 Adenoma tubulovelloso

V5.2
(*) F.S.M.: Fase secretora Menstrual

e-forms Viewer & Transmission

+ : Positivo para el caso
 SSVS Capture
• SSVS captured with the 4x objective

• ROI’s (Region of Interest) selected by

technician, captured with the 20x
objective

• Some clinical data included in each

SSVS
 SSVS – samples
• Small power
enough for
having an
image with
diagnostic
quality
Digital zoom 500x
53MB
1.6x 6.3x

68MB

7.8x 250x
 SSVS - samples
Areas identified by pathologist / technician
Random captured areas

26Mb 16Mb

6x
3x
40x

40x
 SSVS Samples

8Mb 1Mb

42.5x
31.3x

250x

250x
 SSVS Assessment
• 10 pathologists, not trained in
Telepathology

• 3 pathologists, trained in TelePathology

• 9 cytological/histological samples
Evaluation form
 Results – ROC
SSVS - Validity for diagnosis:

• Area under the ROC curve of 0.95 p<0.001, (good diagnostic quality)
 Results - Kappa
Concordance and precision was high for
telepathology trained pathologists
• k=0.73, p<0.001

• Concordance and precision was low for

pathologists non-trained in telepathology
• low k=0.4, p<0.001

• Comments of the users where mainly devoted to

improve the sampling area of the ROI.
 Conclusions
• The SSVS technique allows the technicians to digitize a
virtual slide easy to storage due to its small size.

• SSVS is perfectly suitable for discussion and diagnosis at

distance through intranet and Internet providing a cheap
digital microscope and an online collaborative system.

• For specimens that require high power to make diagnosis,

the SSVS+ROI technique has been proved of value.
Thanks!