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Computational Radiology Laboratory Harvard Medical School www.crl.med.harvard.edu Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts A validation framework for brain tumor segmentation Neculai Archip, Ph.D. Harvard Medical School

Computational Radiology Laboratory Harvard Medical School Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

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Page 1: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology LaboratoryHarvard Medical Schoolwww.crl.med.harvard.edu

Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

A validation framework for brain tumor segmentation

Neculai Archip, Ph.D.

Harvard Medical School

Page 2: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 2

Outline

• Brain image database;

• Existent segmentation data;

• STAPLE;

• How to validate a new algorithm;

• Performance study.

Page 3: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 4

Motivation of Brain Tumor Segmentation: Augmented Visualization in Image Guided Neurosurgery

• Acquire MRI, DT-MRI, fMRI preoperatively– Plan intervention– Enhance tumor

visualization– Better perceive critical

healthy structures

• Align preoperative data with intra-operative configuration of patient

Page 4: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 5

Brain Image database

• Acquisition information: – 10 SPGR T1

– POST GAD resolution: 256x256x124

– pixel size: 0.9375 x 0.9375 mm

– slice thickness: 1.5 mm

– slice gap: 0.0 mm

– acquisition order: LR

case tumor location slice 1 meningioma left frontal 44 2 meningioma left parasellar 58 3 meningioma right parietal 784 low grade glioma left frontal 35 5 astrocytoma right frontal 92 6 low grade glioma right frontal 81 7 astrocytoma right frontal 92 8 astrocytoma left temporal 39 9 astrocytoma left frontotemporal 31 10 low grade glioma left temporal 35

Page 5: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 6

Existent segmentation data

• Manual segmentation performed by 4 independent experts

• low grade glioma

Expert 1 Expert 2 Expert 3 Expert 4

Original Image

Page 6: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 7

One automatic segmentation algorithm

• Kaus et al. – “Adaptive Template Moderated Brain Tumor Segmentation in MRI”, Radiology. 2001;218:586-591

Segmented images

Registration

Statistical Classification

Template Distance Transforms

Brain atlas

Grey value images

Original tumor image

Tumor segmentation performed by Kaus’

method

Page 7: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 8

Validation of Image Segmentation• Spectrum of accuracy versus realism in

reference standard.• Digital phantoms.

– Ground truth known accurately.– Not so realistic.

• Acquisitions and careful segmentation.– Some uncertainty in ground truth.– More realistic.

• Autopsy/histopathology.– Addresses pathology directly; resolution.

• Clinical data ?– Hard to know ground truth.– Most realistic model.

Page 8: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 9

Validation of Image Segmentation

• Comparison to digital and physical phantoms:– Excellent for testing the anatomy, noise and

artifact which is modeled.– Typically lacks range of normal or

pathological variability encountered in practice.

Page 9: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 11

Validation of Image Segmentation

• Comparison to expert performance; to other algorithms:

• What is the appropriate measure for such comparisons ?

• Our new approach:• Simultaneous estimation of hidden ``ground

truth’’ and expert performance.• Enables comparison between and to experts.• Can be easily applied to clinical data exhibiting

range of normal and pathological variability.

Page 10: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 12

STAPLE

• STAPLE (Simultaneous Truth and Performance Level Estimation):– An algorithm for estimating performance

and ground truth from a collection of independent segmentations.

– Warfield, Zou, Wells MICCAI 2002.– Warfield, Zou, Wells, IEEE TMI 2004.

Page 11: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 13

Estimation Problem

• Complete data density:• Binary ground truth Ti for each voxel i.

• Expert j makes segmentation decisions Dij.

• Expert performance characterized by sensitivity p and specificity q.

– We observe expert decisions D. If we knew ground truth T, we could construct maximum likelihood estimates for each expert’s sensitivity (true positive fraction) and specificity (true negative fraction):

)|( qp,TD,f

)|,(lnmaxargˆ,ˆ qp,TDqpqp,

f

Page 12: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 14

Expectation-Maximization• Since we don’t know ground truth T, treat T as a

random variable, and solve for the expert performance parameters that maximize:

• Parameter values θj=[pj qj]T that maximize the conditional expectation of the log-likelihood function are found by iterating two steps:– E-step: Estimate probability of hidden ground truth T

given a previous estimate of the expert quality parameters, and take expectation.

– M-step: Estimate expert performance parameters by comparing D to the current estimate of T.

ˆ ˆ( | ) ln ( | ) |Q E f

θ θ D,T θ D,θ

Page 13: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 15

Validation of a new algorithm

4 manual segmentations

1 automatic segmentation STAPLE

Output of a new segmentation algorithm

Performance assessment

+

Ground truth

Page 14: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 16

A new algorithm• Spectral clustering algorithms:

– Shi and Malik 2000 • NCUT criterion

– Ng, Jordan and Weiss 2002 • Supervised clustering using k eigenvectors

– Miela and Shi 2002• Supervised clustering – connection with Markov Chains

– Fowlkes, Belongie, Chung, Malik 2004 • Nyström method – spine segmentation from MRI

• Fiedler eigenvector based segmentation:– Archip et al. 2005.

• Related approached used in seriation and the consecutive ones problems.

Page 15: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 17

Segmentation as weighted graph partitioning

Pixels i I = vertices of graph GEdges ij = pixel pairs with Sij > 0

Similarity matrix S = [ Sij ]

Given a partition (A,B) of the vertex set V

rjXiX

X

jXiX

I eotherwise

jFiF

ij es2||)()(||,

2

22||)()(||

2

22

,0

)||()(||

),(

),(

),(

),(),(

VBassoc

BAcut

VAassoc

BAcutBANcut

Page 16: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 18

Optimize NCUT

• an approximation is obtained by solving the

generalized eigenvalue problem

for the second smallest generalized eigenvector.

Dyy

ySDyGMinNcut

t

t

y

)(min)(

DyySD )(

Page 17: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 19

The algorithm• P = D-S • P sparse• Py= λy• Lanczos used for efficiency• λ1, λ2 first 2 eigenvalues

– λ1 =1; use λ2 instead

• y1,y2 first 2 eigenvectors– y2 – Fiedler eigenvector

Page 18: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 20

Use Fiedler eigenvector to segment the image

• Sort Fiedler eigenvector with the permutation

• Apply to the image pixels vector

• The new image vector

• Split into compact blocks s.t. components similarity• Complete segmentation – interactively select the cluster

of interest.

),...,( 21 Nii

),...,( 21 NIII

),...,(21 N

ii III

I

Page 19: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 21

Tumor Segmentation Evaluation

  1 2 3 4 KausFiedlerbased

pj 0.867 0.978 0.971 0.908 0.978 0.956

qj 0.999 1.000 0.998 0.999 1.000 0.998

Tumor region Experts STAPLEKaus Fiedler based

Page 20: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 22

Conclusions

• Framework for the validation of brain tumor segmentation: image + software.

• STAPLE public available.

• Image and segmentation data will be made public available.

• Existent data to be added to the image database.

Page 21: Computational Radiology Laboratory Harvard Medical School  Brigham and Women’s Hospital Children’s Hospital Boston Massachusetts

Computational Radiology Laboratory. Slide 23

Acknowledgements

• Simon K. Warfield.• Peter M. Black.• Alexandra Golby.• Ferenc A. Jolesz.• Ron Kikinis.• Lawrence Panych.• Kelly H. Zou.• Steve Haker.• Vicente Grau-Colomer.• Olivier Clatz• Herve Delingette

• Herve Delingette• Nicholas Ayache• Martha Shenton.• Clare Tempany.• Carl Winalski.• Michael Kaus.• William M. Wells.• Andrea Mewes.• Heidelise Als.• Petra Huppi.• Terrie Inder.

Contributors to this research:

www.crl.med.harvard.edu