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Swiss Medical Image Computing Day siemens.ch/answers Automated Detection of WM and Cortical Lesions in Early-Stages of MS Mário João Fartaria Advanced Clinical Imaging Technology (HC CMEA SUI DI BM PI), Siemens Healthcare AG, Lausanne, Switzerland.

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Page 1: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

Swiss Medical Image Computing Day siemens.ch/answers

Automated Detection of WM and Cortical

Lesions in Early-Stages of MS

Mário João Fartaria

Advanced Clinical Imaging Technology (HC CMEA SUI DI BM PI), Siemens Healthcare AG, Lausanne, Switzerland.

Page 2: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 2 Swiss Medical Image Computing Day

Outline

Multiple Sclerosis

Introduction

Methodology and Results

Conclusions

Future Trends

Page 3: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 3 Swiss Medical Image Computing Day

Outline

Multiple Sclerosis

Introduction

Methodology and Results

Conclusions

Future Trends

Page 4: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 4 Swiss Medical Image Computing Day

Multiple Sclerosis

Myelin degeneration

of the brain

Page 5: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 5 Swiss Medical Image Computing Day

Multiple Sclerosis

Non-pathological

tissue Myelin degeneration

of the brain

Page 6: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 6 Swiss Medical Image Computing Day

Multiple Sclerosis

Nerve Cell

Non-pathological

tissue Myelin degeneration

of the brain

Page 7: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 7 Swiss Medical Image Computing Day

Multiple Sclerosis

Nerve Cell

Non-pathological

tissue Myelin degeneration

of the brain

Myelin sheath Nerve fiber

Page 8: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 8 Swiss Medical Image Computing Day

Multiple Sclerosis

Nerve Cell

Non-pathological

tissue Myelin degeneration

of the brain

Myelin sheath Nerve fiber

Exposed

nerve fiber

Damaged

myelin sheath

Page 9: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 9 Swiss Medical Image Computing Day

Multiple Sclerosis

Nerve Cell

Non-pathological

tissue Myelin degeneration

of the brain

Myelin sheath Nerve fiber

Exposed

nerve fiber

Damaged

myelin sheath

MS

LESION

Page 10: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 10 Swiss Medical Image Computing Day

Multiple Sclerosis

Nerve Cell

Non-pathological

tissue Myelin degeneration

of the brain

Myelin sheath Nerve fiber

Exposed

nerve fiber

Damaged

myelin sheath

MS

LESION

Page 11: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 11 Swiss Medical Image Computing Day

Multiple Sclerosis

Nerve Cell

Non-pathological

tissue Myelin degeneration

of the brain

Myelin sheath Nerve fiber

Exposed

nerve fiber

Damaged

myelin sheath

MS

LESION

Page 12: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 12 Swiss Medical Image Computing Day

Outline

Multiple Sclerosis

Introduction

Methodology and Results

Conclusions

Future Trends

Page 13: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 13 Swiss Medical Image Computing Day

MRI

Page 14: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 14 Swiss Medical Image Computing Day

MRI – Brain Tissues

Cerebrospinal Fluid Grey Matter WM Matter

MPRAGE

Page 15: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 15 Swiss Medical Image Computing Day

MRI - Contrasts

MPRAGE FLAIR

DIR MP2RAGE T1map1) MP2RAGE Uniform1)

1)Marques et al. NeuroImage. 2010

Page 16: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 16 Swiss Medical Image Computing Day

MRI in Multiple Sclerosis

Cerebrospinal Fluid Grey Matter WM Matter

FLAIR

Page 17: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 17 Swiss Medical Image Computing Day

MRI in Multiple Sclerosis

Cerebrospinal Fluid Grey Matter WM Matter

FLAIR MS Lesions

Page 18: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 18 Swiss Medical Image Computing Day

MRI – MS Lesions

FLAIR MS Lesions

WM lesions

(pure WM)

Cortical Type I

(across WM/GM)

Cortical Type II

(within the cortex)

Cortical Type III

(sub-pial lesions

over one gyrus)

White Matter Cortex

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2015-11-24, Fartaria M.J.

Page 19 Swiss Medical Image Computing Day

Manual Segmentation - Limitations

Lesions with poor contrast

Time-consuming

Intra-observer variability

Inter-observer variability

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2015-11-24, Fartaria M.J.

Page 20 Swiss Medical Image Computing Day

State-of-the-Art

0

2

4

6

8

10

12

14

16

N.°

of

S

tud

ies

Year of Publication

Automated methods show less agreement with manually segmented scans

than those obtained with segmentations by independent observers2)

2)Garcia-Lorenzo et al. Med image Anal. 2013

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Page 21 Swiss Medical Image Computing Day

State-of-the-Art3)

0

5

10

15

20

25

30

35

Atlas-based Learning from Manual

Segmentation

Unsupervised - Abnormal tissue

Unsupervised - Lesion properties

% o

f S

tud

ies

3)Lladó et al. Information Sciences. 2013

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2015-11-24, Fartaria M.J.

Page 22 Swiss Medical Image Computing Day

Novelty

Lesions

Type I (across WM/GM)

WM

Cortical

• WM and cortical lesion

Segmentation

Type II (whithin the cortex)

Type III (sub-pial lesions over

one gyrus)

Page 23: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 23 Swiss Medical Image Computing Day

Novelty

• WM and cortical lesion

Segmentation

• Applied to patients with

low disability

Page 24: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 24 Swiss Medical Image Computing Day

Novelty

• WM and cortical lesion

Segmentation

• Applied to patients with

low disability

State-of the art

Page 25: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 25 Swiss Medical Image Computing Day

Novelty

• WM and cortical lesion

Segmentation

• Applied to patients with

low disability

State-of the art

Our Study

Page 26: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 26 Swiss Medical Image Computing Day

Novelty

MPRAGE FLAIR

• WM and cortical lesion

Segmentation

• Applied to patients with

low disability

• Explore advanced MRI

contrasts

Clinical

Contrasts

Page 27: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 27 Swiss Medical Image Computing Day

Novelty

MPRAGE FLAIR

MP2RAGE DIR

• WM and cortical lesion

Segmentation

• Applied to patients with

low disability

• Explore advanced MRI

contrasts

Clinical

Contrasts

Advanced

Contrasts4)

4)Kober et al. Investigative Radiology. 2012

Page 28: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 28 Swiss Medical Image Computing Day

Outline

Multiple Sclerosis

Introduction

Methodology and Results

Conclusions

Future Trends

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2015-11-24, Fartaria M.J.

Page 29 Swiss Medical Image Computing Day

MRI protocol

Voxel Size, mm3

FoV, mm3

Acquisition, min.

TR, ms

TE, ms

TI, ms

MPRAGE

1.0 x 1.0 x 1.2

256 x 240 x 160

5:12

2300

2.98

900

MP2RAGE

1.0 x 1.0 x 1.2

256 x 240 x 176

8:22

5000

2.89

700/2500

3D FLAIR

1.0 x 1.0 x 1.2

256 x 240 x 176

6:27

5000

394

1800

3D DIR

1.1 x 1.0 x 1.2

256 x 240 x 160

12:52

10000

218

450/3650

Total Acquisition time, min: 32:53

3T MAGNETOM Trio a

Tim system (Siemens

Healthcare, Germany)

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Page 30 Swiss Medical Image Computing Day

Pipeline5)

Pre-processing

Classification

Post-Processing

Rigid Registration

Skull-striping

Bias field correction

Intensity Normalization

Atlases registration k-Nearest Neighbors

FP reduction

Region Growing

5)Fartaria et al. JMRI. 2015

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Page 31 Swiss Medical Image Computing Day

Pipeline5)

Pre-processing

Classification

Post-Processing

Rigid Registration6)

Skull-striping

Bias field correction

Intensity Normalization

Atlases registration k-Nearest Neighbors

FP reduction

Region Growing

DIR FLAIR MPRAGE

MP2RAGE space

Rigid Registration to

5)Fartaria et al. JMRI. 2015 6)using Elastix. S. Klein et al. IEEE Trans Med Imaging. 2010

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Page 32 Swiss Medical Image Computing Day

Pipeline5)

Pre-processing

Classification

Post-Processing

Rigid Registration6)

Skull-stripping7)

Bias field correction

Intensity Normalization

Atlases registration k-Nearest Neighbors

FP reduction

Region Growing

5)Fartaria et al. JMRI. 2015

7)using Morphobox. Schmitter et al. Neuroimage:Clinical. 2015.

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Page 33 Swiss Medical Image Computing Day

Pipeline5)

Pre-processing

Classification

Post-Processing

Rigid Registration6)

Skull-stripping7)

Bias field correction8)

Intensity Normalization

Atlases registration k-Nearest Neighbors

FP reduction

Region Growing

5)Fartaria et al. JMRI. 2015 8)using module N4ITK from 3DSlicer. Tustison et al. IEEE Trans Med Imaging. 2010.

Bias field

Page 34: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

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Page 34 Swiss Medical Image Computing Day

Pipeline5)

Pre-processing

Classification

Post-Processing

Rigid Registration6)

Skull-stripping7)

Bias field correction8)

Intensity Normalization9)

Atlases registration k-Nearest Neighbors

FP reduction

Region Growing

5)Fartaria et al. JMRI. 2015

9)Nyul et al. IEEE Trans Med Imaging. 2000.

Voxel Intensity

Subject A

Subject B

Subject C

Voxel Intensity

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Page 35 Swiss Medical Image Computing Day

Pipeline5)

Pre-processing

Classification

Post-Processing

Rigid Registration6)

Skull-stripping7)

Bias field correction8)

Intensity Normalization9)

Atlases10) registration

k-Nearest Neighbors

FP reduction

Region Growing

5)Fartaria et al. JMRI. 2015

10)ICBM 452 T1 Atlas.

MP2RAGE space

Template space Non-rigid

Registration

WM GM CSF

Page 36: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

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Page 36 Swiss Medical Image Computing Day

Pipeline5)

Pre-processing

Classification

Post-Processing

Rigid Registration6)

Skull-stripping7)

Bias field correction8)

Intensity Normalization9)

Atlases10) registration k-Nearest Neighbors

FP reduction

Region Growing

Feature Extraction:

- Voxel intensities

- Spatial location11)

- Tissue PRIORs12)

k-NN, Voxel-wise Classification

Training Set:

• Features

• Labels (Manual Segmentations)

Lesion Probability Mask

5)Fartaria et al. JMRI. 2015

11)Anbeek et al. Neuroimage. 2004; 12)Steenwijk et al. Neuroimage:Clinical. 2013;

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Page 37 Swiss Medical Image Computing Day

Pipeline5)

Pre-processing

Classification

Post-Processing

Rigid Registration6)

Skull-stripping7)

Bias field correction8)

Intensity Normalization9)

Atlases10) registration k-Nearest Neighbors

False-positive reduction

Region Growing

Single voxels classified

as lesion are removed

5)Fartaria et al. JMRI. 2015

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2015-11-24, Fartaria M.J.

Page 38 Swiss Medical Image Computing Day

Pipeline5)

Pre-processing

Classification

Post-Processing

Rigid Registration6)

Skull-stripping7)

Bias field correction8)

Intensity Normalization9)

Atlases10) registration k-Nearest Neighbors

False-positive reduction

Region Growing

Processing Time: ≈ 25 min, (not optimized)

Stop criteria

based on

MP2RAGE

intensities

5)Fartaria et al. JMRI. 2015

Page 39: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

2015-11-24, Fartaria M.J.

Page 39 Swiss Medical Image Computing Day

Data

39 MS patients

25♀14♂

median 34, range 20 - 60

Relapsing-Remitting MS

<5 years from diagnosis (early-stages)

median 1.5, range 1 - 2

Sex

Age

Type of MS

Disease duration

EDSS score

Page 40: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

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Page 40 Swiss Medical Image Computing Day

Validation

Contribution of Advanced MRI Contrasts:

Clinical protocol:

• 3D FLAIR

• 3D FLAIR + MPRAGE

Advanced Protocol:

• 3D FLAIR + MP2RAGE

• 3D FLAIR + MPRAGE + DIR

• 3D FLAIR + MP2RAGE + DIR

Method:

“Leave-one-out” cross validation on 39 subjects

Ground Truth:

• Manual Segmentations

Metrics:

• Detection rate – number of detected lesions per brain

• Dice Similarity Coefficient – overlap measure

Page 41: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

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Page 41 Swiss Medical Image Computing Day

Segmentation Results

Type of Lesion Manual

Segmentation

Automatic

Detection

Automatic

Segmentation

White Matter

Type I

(across WM/GM)

Type II

(within the cortex)

Type III

(sub-pial lesions

over one gyrus)

Co

rtic

al L

esio

ns

MP2RAGE

Page 42: Automated Detection of WM and Cortical Lesions in Early ... · 2015-11-24, Fartaria M.J. Page 29 Swiss Medical Image Computing Day MRI protocol Voxel Size, mm3 FoV, mm3 Acquisition,

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Page 42 Swiss Medical Image Computing Day

Segmentation Results

Manual Segmentation Automatic Segmentation

MP2RAGE 3D FLAIR

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Page 43 Swiss Medical Image Computing Day

Detection Rate WM lesions

Acquisition Time,

min.

6:27 11:39 14:49 24:31 27:41

FLAIR FLAIR

MPRAGE

FLAIR

MP2RAGE

FLAIR

MPRAGE

DIR

FLAIR

MP2RAGE

DIR

Dete

cti

on

Rate

Good Detection Rate: FLAIR + MPRAGE (Clinical Protocol)5) 5)Fartaria et al. JMRI. 2015

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Page 44 Swiss Medical Image Computing Day

Detection Rate – Cortical lesions

FLAIR FLAIR

MPRAGE

FLAIR

MP2RAGE

FLAIR

MPRAGE

DIR

FLAIR

MP2RAGE

DIR

Dete

cti

on

Rate

Acquisition Time,

min.

6:27 11:39 14:49 24:31 27:41

Best Detection Rate: FLAIR + MPRAGE/MP2RAGE + DIR (Advanced Protocol)5)

5)Fartaria et al. JMRI. 2015

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Page 45 Swiss Medical Image Computing Day

Results – All type of lesions

FLAIR FLAIR

MPRAGE

FLAIR

MP2RAGE

FLAIR

MPRAGE

DIR

FLAIR

MP2RAGE

DIR

Dic

e S

imil

ari

ty

Co

eff

icie

nt

Acquisition Time,

min.

6:27 11:39 14:49 24:31 27:41

Overlap improvement : FLAIR + MPRAGE/MP2RAGE + DIR (Advanced Protocol)5)

5)Fartaria et al. JMRI. 2015

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Page 46 Swiss Medical Image Computing Day

Comparison with other Published Methods

LesionTOADS14) LST – SPM13)

13)Shiee et al. NeuroImage. 2015 14)Schmidt et al. NeuroImage. 2015

Only applied for WM lesion segmentation

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Page 47 Swiss Medical Image Computing Day

Comparison with other Published Methods

Manual Segmentation Our Method LST – SPM13) LesionTOADS14)

13)Shiee et al. NeuroImage. 2015 14)Schmidt et al. NeuroImage. 2015

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Page 48 Swiss Medical Image Computing Day

Comparison with other Published Methods

13)Shiee et al. NeuroImage. 2015 14)Schmidt et al. NeuroImage. 2015

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Page 49 Swiss Medical Image Computing Day

Outline

Multiple Sclerosis

Introduction

Methodology and Results

Conclusions

Future Trends

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Page 50 Swiss Medical Image Computing Day

Conclusions

• Method for WM and cortical lesion detection/segmentation based on advanced MRI

• FLAIR + advanced sequences: best detection rate for WM and cortical lesions

• Advanced sequences : long acquisition time (DIR, ca. 12:52 min)

• Clinical protocol (FLAIR + MPRAGE): Good detection rate for WM lesions

• Advanced protocol improves the overlap metric:

True Positives

False Positives

• Challenges in cortical lesion detection:

Low number of lesions

Small size

Affected by partial volume (location at WM/GM interface)

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Page 51 Swiss Medical Image Computing Day

Outline

Multiple Sclerosis

Introduction

Methodology and Results

Conclusions

Future Trends

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2015-11-24, Fartaria M.J.

Page 52 Swiss Medical Image Computing Day

Longitudinal Assessment

Time Point 2 (TP2) Time Point 2 (TP2)

2 YEARS

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Page 53 Swiss Medical Image Computing Day

Longitudinal Assessment

TP1

New Enlarged Resolved Shrunken Unaltered

Lesion Mask TP1 TP2 Lesion Mask TP1 TP2

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Ultra-high field MRI (7T)

TP1 TP2

WM lesion Cortical Lesion Type I

Cortical Lesion Type II Cerebellum lesion in the folia

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The Team

Advanced Clinical Imaging Technology (ACIT)

• Tobias Kober

• Gunnar Krueger

• Alexis Roche

• Bénédicte Maréchal

• Davide Picinni

• Guillaume Bonnier

• Tom Hilbert

• Pavel Falkovskiy

• Maryna Babayeva

•Théo Galy-Fajou

• Emilie Mussard

• Jannik Schildknecht

Massachusetts General Hospital and Harvard

Medical School

• Cristina Granziera

Medical Image Analyses Laboratory (MIAL)

• Meritxell Bach Cuadra

• Elena Najdenovska

• Carlos Ciller

• Sébastien Tourbier