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Translational Health Research

         Cervical cancer
Translational health research
http://www.thelancet.com/
YESTERDAY
In 1940s, cervical cancer was a major cause of death among women of childbearing age
in the United States.

TODAY
Cervical cancer  once one of the most common cancers affecting U.S. women  now
ranks 14th in frequency. Because precancerous lesions found by Pap smears can be
treated and cured before they develop into cancer, and because cervical cancer is often
detected before it becomes advanced, the incidence and death rates for this disease are
relatively low.

HOW?
Better visualization:- Introduction Papanicolaou (Pap) smear test in which a sample of
cervical cells is examined under a microscope to detect cellular abnormalities. The
incidence of invasive cervical cancer declined dramatically. Between 1955 and 1992,
U.S. cervical cancer incidence and death rates declined by more than 60%. and
automation
Automation:- Introduction of ThinPrep速, FocalPoint速 (FDA approved) systems which
screens and suggest potential cases to cytopathologists



                        http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=76
                         http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=76
Cancer Facts and Figures 2012 America cancer society
Why cant I just mimic
the existing technology?
Experinced Cytopathologists
COST
Accuracy (False neg.)
Massive screening             OUR CONCERN
Automated imaging
Computational Facility
Extension to rural areas
Business Model
Awareness
.
.
Translational health research
Monolayer Preparation
 Collection of cervical smears from transformation zone and endo
cervix by Ayers spatula and endo-cervical brush respectively into
polysol solution.

  Centrifugation at 2000-4000 rpm for 5 mins, supernatant
discarded and re-suspension of pallet in fresh polysol solution

 Preparation of cervical monolayer smear using cyto-centrifuge
with appropriate funnel and filter cards.

 Fixation of the smear with 95% ethanol for 10 mins.

  Pap staining of the monolayer cervical smear using hematoxylin
(stains nucleus blue), orange G (stains cytoplasm of superficial
cells pink) and eosine-azure (stains cytoplasm of intermediate
cells blue to green)

                                                                 9
Feature Identification &
           Significance
No.              Nuclear Feature               Significance
1                Brightness of Nucleus         Most Significant

2                Area of Nucleus               Significant

3                Irregularity of the Nuclear   Significant
                 Membrane

4                Nucleus Roundness             Significant

5                Size of Chromatin Granule     Significant



    Table shows the importance of feature significance in 40 X
    magnification
                                                                  12
Presence of Variations in
        Normal Nuclei




A set of normal nuclei cropped from images of size 2048 x 1536.
Magnification 40X.

                                                                  13
Presence of Variations in
     Abnormal Nuclei




A set of abnormal nuclei. Image size 404 x 270. Courtesy by International
Agency for Research on Cancer cervical cells image database.
Magnification 40X
                                                                        14
Ambiguity in Nuclear
           Features

                a         b           c   d
a.Malignant Intermediate Cell Nucleus.
b.Normal Parabasal Cell Nucleus
c.Malignant Superficial Cell Nucleus.
d.Normal Parabasal Cell Nucleus




                                              15
Implementating out of box
Features and Classification

                                    Classification
                                    Classification


                     Feature
                     Feature
                   Quantification
                   Quantification

    Feature
     Feature
  Identification
  Identification




                                                     16
Nucleus Localization &
          Segmentation
A three phase technique is adopted for segmentation of
nucleus.




                                                         17
Color Imbalance
   As we are intend to implement color image
    processing , there should be no disruptions
    in color cue
 Sources of description
a) Light source (temperature dependent)
b) Digital camera (biasing of any one channel of
    R,G,B)

                                                   CIE standard Color gamut
                                                   provided and limitation of
                                                   screen display




                                                                                18
White Balancing Cont.



Pap stained image of a Normal              Pap stained image of a Abnormal
smear under microscope at 40x              smear under microscope at 40x


                           White Balancing Step




                          White Balanced Images

                                                                             19
Image Enhancement




 Top two images are white balanced. Bottom two are enhanced with CLAHE



                                                                         20
Haematoxyline Probability
Plane




                            21
Segmentaion performance
   Level set
   Method


Morphological
  filtering




                Bilateral Initial    Color  Original L Plane Saturation
                Filtered Mask        Deconv image of Lab        +
                                                     Color Intensity
                image                output
                                                          space   22
      https://www.dropbox.com/sh/p2kt9e181mdx9eh/NfHrVzhrTC
Results of Active
Contour(Level Sets)




                      23
24
Segmented results
25
Segmented results
Target Features of the nucleus for
           computer assisted diagnosis
1.    Area                                         1. Mean value of Blue color value on
2.    Perimeter
                                                       nucleus
                                                   2. Entropy of red color values of nucleus
3.    ConvexArea
                                                   3. Entropy of Green color values of
4.    Filled area                                      nucleus
5.    Eccentricity                                 4. Entropy of Blue color values of
6.    MajorAxisLength                                  nucleus
7.    MinorAxisLength                              5. contrast of gray values of nucleus
8.    EquivDiameter                                6. correlation of gray values of nucleus
9.    MinorAxisLength                              7. energy homogeneity of gray values of
                                                       nucleus
10.   Standard deviation of Red color values on
      nucleus
                                                   8. standard deviation of Laws mask
                                                       response
11.   Mean value of Red color value on nucleus     9. mean of Laws mask response
12.   Standard deviation of Green color values     10. standard deviation of LBP(local
      on nucleus                                       binary pattern) response
13.   Mean value of Green color value on           11. mean of LBP response
      nucleus
14.   Standard deviation of Blue color values on
      nucleus                                                                             26
SVM based classification for 25 nuclear features




                                               28

More Related Content

Translational health research

  • 4. YESTERDAY In 1940s, cervical cancer was a major cause of death among women of childbearing age in the United States. TODAY Cervical cancer once one of the most common cancers affecting U.S. women now ranks 14th in frequency. Because precancerous lesions found by Pap smears can be treated and cured before they develop into cancer, and because cervical cancer is often detected before it becomes advanced, the incidence and death rates for this disease are relatively low. HOW? Better visualization:- Introduction Papanicolaou (Pap) smear test in which a sample of cervical cells is examined under a microscope to detect cellular abnormalities. The incidence of invasive cervical cancer declined dramatically. Between 1955 and 1992, U.S. cervical cancer incidence and death rates declined by more than 60%. and automation Automation:- Introduction of ThinPrep速, FocalPoint速 (FDA approved) systems which screens and suggest potential cases to cytopathologists http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=76 http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=76
  • 5. Cancer Facts and Figures 2012 America cancer society
  • 6. Why cant I just mimic the existing technology?
  • 7. Experinced Cytopathologists COST Accuracy (False neg.) Massive screening OUR CONCERN Automated imaging Computational Facility Extension to rural areas Business Model Awareness . .
  • 9. Monolayer Preparation Collection of cervical smears from transformation zone and endo cervix by Ayers spatula and endo-cervical brush respectively into polysol solution. Centrifugation at 2000-4000 rpm for 5 mins, supernatant discarded and re-suspension of pallet in fresh polysol solution Preparation of cervical monolayer smear using cyto-centrifuge with appropriate funnel and filter cards. Fixation of the smear with 95% ethanol for 10 mins. Pap staining of the monolayer cervical smear using hematoxylin (stains nucleus blue), orange G (stains cytoplasm of superficial cells pink) and eosine-azure (stains cytoplasm of intermediate cells blue to green) 9
  • 10. Feature Identification & Significance No. Nuclear Feature Significance 1 Brightness of Nucleus Most Significant 2 Area of Nucleus Significant 3 Irregularity of the Nuclear Significant Membrane 4 Nucleus Roundness Significant 5 Size of Chromatin Granule Significant Table shows the importance of feature significance in 40 X magnification 12
  • 11. Presence of Variations in Normal Nuclei A set of normal nuclei cropped from images of size 2048 x 1536. Magnification 40X. 13
  • 12. Presence of Variations in Abnormal Nuclei A set of abnormal nuclei. Image size 404 x 270. Courtesy by International Agency for Research on Cancer cervical cells image database. Magnification 40X 14
  • 13. Ambiguity in Nuclear Features a b c d a.Malignant Intermediate Cell Nucleus. b.Normal Parabasal Cell Nucleus c.Malignant Superficial Cell Nucleus. d.Normal Parabasal Cell Nucleus 15
  • 14. Implementating out of box Features and Classification Classification Classification Feature Feature Quantification Quantification Feature Feature Identification Identification 16
  • 15. Nucleus Localization & Segmentation A three phase technique is adopted for segmentation of nucleus. 17
  • 16. Color Imbalance As we are intend to implement color image processing , there should be no disruptions in color cue Sources of description a) Light source (temperature dependent) b) Digital camera (biasing of any one channel of R,G,B) CIE standard Color gamut provided and limitation of screen display 18
  • 17. White Balancing Cont. Pap stained image of a Normal Pap stained image of a Abnormal smear under microscope at 40x smear under microscope at 40x White Balancing Step White Balanced Images 19
  • 18. Image Enhancement Top two images are white balanced. Bottom two are enhanced with CLAHE 20
  • 20. Segmentaion performance Level set Method Morphological filtering Bilateral Initial Color Original L Plane Saturation Filtered Mask Deconv image of Lab + Color Intensity image output space 22 https://www.dropbox.com/sh/p2kt9e181mdx9eh/NfHrVzhrTC
  • 24. Target Features of the nucleus for computer assisted diagnosis 1. Area 1. Mean value of Blue color value on 2. Perimeter nucleus 2. Entropy of red color values of nucleus 3. ConvexArea 3. Entropy of Green color values of 4. Filled area nucleus 5. Eccentricity 4. Entropy of Blue color values of 6. MajorAxisLength nucleus 7. MinorAxisLength 5. contrast of gray values of nucleus 8. EquivDiameter 6. correlation of gray values of nucleus 9. MinorAxisLength 7. energy homogeneity of gray values of nucleus 10. Standard deviation of Red color values on nucleus 8. standard deviation of Laws mask response 11. Mean value of Red color value on nucleus 9. mean of Laws mask response 12. Standard deviation of Green color values 10. standard deviation of LBP(local on nucleus binary pattern) response 13. Mean value of Green color value on 11. mean of LBP response nucleus 14. Standard deviation of Blue color values on nucleus 26
  • 25. SVM based classification for 25 nuclear features 28

Editor's Notes

  • #17: Microsoft Engineering Excellence Microsoft Confidential