image analysis for neuroblastoma classification: hysteresis thresholding for nuclei segmentation...

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Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1 , PhD Tony Pan 1 , MS Hiro Shimada 2 , MD, PhD Joel Saltz 1 , MD, PhD 1 Department of Biomedical Informatics, The Ohio State University, Columbus, OH 2 Children’s Hospital, Los Angeles, CA [email protected] www.bmi.osu.edu

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Page 1: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for

Nuclei Segmentation

Metin Gurcan1, PhDTony Pan1, MS

Hiro Shimada2, MD, PhDJoel Saltz1, MD, PhD

1Department of Biomedical Informatics, The Ohio State University, Columbus, OH2Children’s Hospital, Los Angeles, CA

[email protected]

Page 2: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

CAD

• Computer-aided diagnosis: – a diagnosis made by a

physician using the output of a computerized system

• Computerized system– Automated image (or

data) analysis

Page 3: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Applications

• Breast Cancer

• Lung Cancer

• Colon Cancer

Page 4: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Observational Lapses

• Fatigue• Distraction• Emotional stress• Satisfaction of Search• Variation in reader

Page 5: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

CAD

CAD

Physician Decision

Page 6: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Breast Cancer

M. N. Gurcan, B. Sahiner, H. P. Chan, L. Hadjiiski, and N. Petrick, "Selection of an optimal neural network architecture for computer-aided detection of microcalcifications--comparison of automated optimization techniques," Med Phys, vol. 28, pp. 1937-48, 2001.

Page 7: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Lung Cancer

M. N. Gurcan, B. Sahiner, N. Petrick, H. P. Chan, E. A. Kazerooni, P. N. Cascade, and L. Hadjiiski, "Lung nodule detection on thoracic computed tomography images: preliminary evaluation of a computer-aided diagnosis system," Med Phys, vol. 29, pp. 2552-8, 2002.

Page 8: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Nodule Segmentation

HR 2 (7/23/01)

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M. N. Gurcan, B. H. Allen, S. K. Rogers, D. Dozer, R. Burns, and J. Hoffmeister, "Accurate nodule volume estimation from helical CT images: Comparison of slice-based and volume-based methods," 88th Scientific Assembly and Annual Meeting of Radiological Society of North

America (RSNA), 2002.

Page 9: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Polyp Segmentation

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5 6 7 8

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M. Gurcan, R. Ernst, A. Oto, S. Worrell, J. Hoffmeister, and S. K. Rogers, "Measurement of colonic polyp size from virtual colonoscopy studies: Comparison of manual and automated methods," SPIE Medical Imaging Conference, vol. 6144, 2006.

Page 10: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Measurement

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M. Gurcan, R. Ernst, A. Oto, S. Worrell, J. Hoffmeister, and S. K. Rogers, "Measurement of colonic polyp size from virtual colonoscopy studies: Comparison of manual and automated methods," SPIE Medical Imaging Conference, vol. 6144, 2006.

Page 11: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

NB Image Analysis

Image Analysis

Pathologist Decision

Page 12: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

NB Image Analysis

Image Analysis

Pathologist Decision

Page 13: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Neuroblastoma Classification

• Stroma Density• Differentiation• Mitosis Karyorrhexis

Index

Page 14: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Identify stroma density

Stroma poor Stroma rich Stroma dominant

Composite:

Stroma-

Poor

Rich

Dominant

Page 15: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Identify differentiation

Undifferentiated Poorly differentiated

Differentiating

Page 16: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

MKI Calculation

Low MKI Intermediate

MKI

High

MKI

Page 17: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

How to determine MKI?

• The number of the tumor cells in mitosis and karyorrhexis per 5000 NB cells by averaging

• Darker nuclei with irregular, fragmented shapes– This is how they are separated from hyperchromatic

nuclei, which are more roundish uniformly dark cells (dying a silent death)

• Karyorrhexis cells usually have dark pinkish cytoplasm

• Three types– Low ( < 100 / 5000)– Intermediate( 100-200 / 5000 )– High ( > 200 / 5000 )

Page 18: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

FlowchartH&E Stained

Image

Color Space Decomposition

Morphological Reconstruction

SegmentedNuclei

Post Processing

Hysteresis Thresholding

Page 19: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Original Region of Interest

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H&E Stained Image

Color Space Decomposition

Morphological Reconstruction

SegmentedNuclei

Post Processing

Hysteresis Thresholding

Page 20: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Complement of the R planeH&E Stained

Image

Color Space Decomposition

Morphological Reconstruction

SegmentedNuclei

Post Processing

Hysteresis Thresholding

Page 21: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Output of the Reconstruction Filter

H&E Stained Image

Color Space Decomposition

Morphological Reconstruction

SegmentedNuclei

Post Processing

Hysteresis Thresholding

Page 22: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Top-hat by ReconstructionH&E Stained

Image

Color Space Decomposition

Morphological Reconstruction

SegmentedNuclei

Post Processing

Hysteresis Thresholding

Page 23: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Hysteresis Thresholding

Th

Tl

H&E Stained Image

Color Space Decomposition

Morphological Reconstruction

SegmentedNuclei

Post Processing

Hysteresis Thresholding

Page 24: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Hysteresis Thresholding

Th

Tl

H&E Stained Image

Color Space Decomposition

Morphological Reconstruction

SegmentedNuclei

Post Processing

Hysteresis Thresholding

Page 25: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Segmented Nuclei

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H&E Stained Image

Color Space Decomposition

Morphological Reconstruction

SegmentedNuclei

Post Processing

Hysteresis Thresholding

Page 26: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Watershed SegmentationH&E Stained

Image

Color Space Decomposition

Morphological Reconstruction

SegmentedNuclei

Post Processing

Hysteresis Thresholding

Page 27: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Output of Final Segmentation

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H&E Stained Image

Color Space Decomposition

Morphological Reconstruction

SegmentedNuclei

Post Processing

Hysteresis Thresholding

Page 28: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Segmentation Example

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Page 29: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Segmentation Example

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Page 30: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Segmentation Example

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Page 31: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Segmentation Example

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Page 32: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Segmentation Evaluation

||

||1 AM

AMOS

2||

2

AM

AMOS

M

A

Page 33: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Experimental Results

Without Hysteresis Thresholding

With

Hysteresis Thresholding

OS1 85.76%±14.05% 90.24%±5.14%

OS2 91.56%±10.39 94.79%±2.97%

Page 34: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Summary

• Feasible to do cell segmentation using morphological operations

• Hysteresis Thresholding improves segmentation accuracy while decreasing variability

Page 35: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Summary

• Application of segmentation algorithm to neuroblastoma classification– MKI calculation

Page 36: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Acknowledgment

• Thomas Barr, Columbus Children’s Hospital

• Dr. Hideki Sano, Los Angeles Children’s Hospital

Page 37: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Questions?

Page 38: Image Analysis for Neuroblastoma Classification: Hysteresis Thresholding for Nuclei Segmentation Metin Gurcan 1, PhD Tony Pan 1, MS Hiro Shimada 2, MD,

Select a ROI

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