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07-06-2013
1
Rikke Riber-Hansen MD, PhD Institute of Pathology
Digital image analysis as a catalyst for applied stereology
The digital image analysis
Definition Extraction of meaningful information from digital images by dedicated computer software
HER-21
1 Brügmann et all
Ki67/MART-12
1 Nielsen et all
The digital image analysis process
Preprocess Enhance structures of interest, i.e. nuclei or colour Suppress noise
The digital image analysis process
Segmentation Into the relevant components, i.e. nuclei versus non-nuclei, or IHC positive versus IHC negative
The digital image analysis process
Postprocessing Refining the segmentation
Segmentation
Is often predominantly based on differences in colour
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Segmentation by colour Segmentation by colour
Pitfalls
Holes
Folds
Ink
Unspecific staning
Immunohistochemical requirements
Sensitivity Specificity Optimisation
Stability over time Riber-Hansen et al. APMIS 2012; 120(4):276-89
Begelman et al. IEEE Trans Med Imaging 2009:28;1317-1324
Colour spectrums overlap
DAB
Haematoxylin
Immunohistochemical requirements
Tuominen VJ, Ruotoistenmaki S, Viitanen A, Jumppanen M, Isola J. Breast Cancer Rec. 2010;12:R56
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Why digital image analysis?
Workload reduction
Reduced inter/intraobserver
variation
Quantitiative results
Requirements for new tests
Analytical validity: How accurately does the test measure the feature of interest? Clinical validity: How well does the test predict the outcome of interest?
Example no. 1
Metastasis size: a known prognostic factor in melanoma, and breast cancer
A quick estimate of size
Metastasis diameter
Metastasis diameter and outcome
van der Plough et al. JCO 2011;16:2206-2214
Clinical validity
Can it be reproduced?
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HE S-100 HBM-45
ICC = 0.88
Does this make this analytically valid?
Analytical validity: How accurately does the test measure the feature of interest?
So reproducibility does not guarantee analytical validity
=
Problem no. 1
Tota
l met
asta
tic
volu
me
Solution: Stereology
No. of steps Max
imu
m m
eta
stas
is d
iam
eter
No. of steps
Riber-Hansen R et al. Cancer 2009: 115; 2177-2187
A quick estimate of size
Metastasis diameter
Clinically valid Analytically invalid
Problem: Workload + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + +
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Solution
Digital image analysis based on a stereological measurement: the total metastatic volume
Clinical validity – unpublished data
Example no. 2
Nielsen PS et al. Modern Pathology 2012
Ki67/MART-1
Manual stereology
What did the digital image analysis add?
Nielsen PS et al. Arch Pathol Lab Med. 2012:136;627-634
New prognostic markers
Digital image analysis may act as a high-throughput device to examine multiple stereologically sound ways of quantification for a given marker.
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Conclusions
Digital image analysis
Is versatile Requires high quality sections and staining Is sensitive to suboptimal haematoxylin staining Needs to be taken into account from the onset of the study Should be based on stereologically sound estimates