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G R O U P - W I S E A N A LY S I S O N M Y E L I N AT I O N
P R O F I L E S O F C E R E B R A L C O R T E X U S I N G T H E
S E C O N D E I G E N V E C T O R O F L A P L A C E - B E LT R A M I
O P E R AT O R
S E U N G - G O O K I M , J O H A N N E S S T E L Z E R , P I E R R E - L O U I S B A Z I N
A D R I A N V I E H W E G E R , T H O M A S K N Ö S C H E
ISBI 2014, 1st of May, Beijing, China
O V E R V I E W
• Aim: Intersubject correspondence for group-wise
analysis on myelination profiles from the high-field MRI
O V E R V I E W
• Aim: Intersubject correspondence for group-wise
analysis on myelination profiles from the high-field MRI
• Method: Parametrization using the second Laplace-
Beltrami eigenvector
O V E R V I E W
• Aim: Intersubject correspondence for group-wise
analysis on myelination profiles from the high-field MRI
• Method: Parametrization using the second Laplace-
Beltrami eigenvector
• Application: Statistical inference using random field
theory on Heschl’s gyrus in auditory cortex
M Y E L I N AT I O N P R O F I L E
A N D I N - V I V O I M A G I N G
I N T R O D U C T I O N & M O T I VA T I O N
M Y E L O A R C H I T E C T U R E O F C O R T E X
(cc) Quasar Jarosz
Beck (1928) G M
W M
M Y E L O A R C H I T E C T U R E O F C O R T E X
Nieuwenhuys (2013) Ed. Geyer & Turner
(cc) Quasar Jarosz
Vogt (1903)
C Y T O - M Y E L O -
Beck (1928) G M
W M
M Y E L O A R C H I T E C T U R E O F C O R T E X
Nieuwenhuys (2013) Ed. Geyer & Turner
(cc) Quasar Jarosz
Vogt (1903)
C Y T O - M Y E L O -
Beck (1928) G M
W M
M Y E L O A R C H I T E C T U R E O F C O R T E X
Nieuwenhuys (2013) Ed. Geyer & Turner
(cc) Quasar Jarosz
Hopf (1954)
Vogt (1903)
C Y T O - M Y E L O -
Beck (1928) G M
W M
M Y E L O A R C H I T E C T U R E O F C O R T E X
Nieuwenhuys (2013) Ed. Geyer & Turner
(cc) Quasar Jarosz
Hopf (1954)
I N - V I V O I M A G I N G O F I N T R A C O R T I C A L
M Y E L O A R C H I T E C T U R E U S I N G 7 T M R I
• Quantitative T1
mapping (qT1)
• T1 inversely
correlates with
myelination
• Myelin is the main
contribution to the T1
contrast [1]
Geyer et al. (2011) Front Hum Neurosci
ex-vivo
in-vivo
[1] Eickhoff et al. (2005) Hum Brain Mapp
I N T E R S U B J E C T C O R R E S P O N D E N C E
C S F G M W M
I N T E R S U B J E C T C O R R E S P O N D E N C E
C S F G M W M
W H O L E B R A I N R E G I S T R AT I O N ?
• Not yet fully developed for
high-field MRIs
• Signal loss in ventral
regions
• Different image contrast
(quantitative T1 mapping)
• Dimensionality from 

sub-mm resolution
M O T I VAT I O N : C O R R E S P O N D E N C E
• To construct correspondence between myelination
profiles in order to infer group-wise differences
• Circumventing whole-brain registration issues
• More precise than averaging within a ROI
M O T I VAT I O N : C O R R E S P O N D E N C E
• To construct correspondence between myelination
profiles in order to infer group-wise differences
• Circumventing whole-brain registration issues
• More precise than averaging within a ROI
• Parametrization using the second Laplace-Beltrami
eigenvector
Lévy (2006) SMI
T H E S E C O N D L A P L A C E - B E LT R A M I
E I G E N V E C T O R
• Monotonous increase along the longest
geodesic distance
T H E S E C O N D L A P L A C E - B E LT R A M I
E I G E N V E C T O R
• Monotonous increase along the longest
geodesic distance
• Used to construct medial axes & Reeb
graph for arbitrarily shaped structures
Seo et al. (2011) SPIE
Shi et al. (2008) MICCAIShi et al. (2008) IEEE CVPR
Reuter et al. (2009) CAD
A P P L I C AT I O N : H E S C H L’ S G Y R U S ( H G )
A P P L I C AT I O N : H E S C H L’ S G Y R U S ( H G )
A I L P
Wallace et al. (2002) Exp Brain Res
A I
L P
S TA
M Y E L I N AT I O N P R O F I L E
E S T I M AT I O N
P R E P R O C E S S I N G
S U B J E C T S & I N - V I V O I M A G I N G
• Six healthy participants: all male, age=25 ± 2 y.o.
• MP2RAGE (magnetization-prepared rapid gradient
echo with two inversion times) at 0.7 mm isovoxel
using a 7 T scanner (Siemens)
Marques et al. (2010) NeuroImage
qT1T1w
T1w at 1mm isovoxel
T1w at 1mm isovoxel
qT1 at 0.7 mm isovoxel
T1w at 1mm isovoxel
qT1 at 0.7 mm isovoxel
Regenerated surfaces
M A N U A L D E L I N E AT I O N O F H G
• Duplication/sulcus (10) • Single HG (LH:1, RH:1)
R E A L I S T I C C O R T I C A L L AY E R I N G [ 1 ]
[1] Waehnert et al. (2013) NeuroImage
R E A L I S T I C C O R T I C A L L AY E R I N G [ 1 ]
http://www.cbs.mpg.de/institute/software/cbs-hrt[1] Waehnert et al. (2013) NeuroImage
T H E S E C O N D L A P L A C E -
B E LT R A M I E I G E N V E C T O R
PA R A M E T E R I Z A T I O N & I N F E R E N C E
• Laplace-Beltrami (LB) operator 𝚫 of function 𝒇 defined on an
arbitrary manifold is given by:
L A P L A C E - B E LT R A M I E I G E N V E C T O R S
D f := div(grad f)
M 2 R2
⇢ R3
• To find eigenvector Ѱj and eigenvalue 𝝀j of LB, solve:
0 = l0 < l1  l2  ···
y0,y1,y2 ···
• Laplace-Beltrami (LB) operator 𝚫 of function 𝒇 defined on an
arbitrary manifold is given by:
L A P L A C E - B E LT R A M I E I G E N V E C T O R S
D f := div(grad f)
M 2 R2
⇢ R3
Dyj = ljyj
• To find eigenvector Ѱj and eigenvalue 𝝀j of LB, solve:
0 = l0 < l1  l2  ···
y0,y1,y2 ···
• Laplace-Beltrami (LB) operator 𝚫 of function 𝒇 defined on an
arbitrary manifold is given by:
L A P L A C E - B E LT R A M I E I G E N V E C T O R S
D f := div(grad f)
[1] Qui et al., (2006) TMI; [2] Aubry et al. (2011) ICCV
CY = lAY C Cotagent matrix
A Mass matrix
• Discretization of LB using FEM, then the eigenvectors can be
computed from generalized eigenvalue problem [1,2]:
M 2 R2
⇢ R3
Dyj = ljyj
• To find eigenvector Ѱj and eigenvalue 𝝀j of LB, solve:
0 = l0 < l1  l2  ···
y0,y1,y2 ···
• Laplace-Beltrami (LB) operator 𝚫 of function 𝒇 defined on an
arbitrary manifold is given by:
L A P L A C E - B E LT R A M I E I G E N V E C T O R S
D f := div(grad f)
[1] Qui et al., (2006) TMI; [2] Aubry et al. (2011) ICCV
CY = lAY C Cotagent matrix
A Mass matrix
• Discretization of LB using FEM, then the eigenvectors can be
computed from generalized eigenvalue problem [1,2]:
http://www.di.ens.fr/~aubry/wks.html
*smoothed for visualization
M 2 R2
⇢ R3
Dyj = ljyj
L E V E L S E T S B A S E D O N L B 2
PA R A M E T E R I Z E D M Y E L I N P R O F I L E S
C S F
G M
W M
AV E R A G E D M Y E L I N I M A G E S
Left Right
1st
2nd
2315
2827
Corticaldepth
AL PM
0
0.5
1
2435
2773
Corticaldepth
AL PM
0
0.5
1
2493
2762
Corticaldepth
AL PM
0
0.5
1
2543
2833
Corticaldepth
AL PM
0
0.5
1
T1 (ms)
AV E R A G E D M Y E L I N I M A G E S
Left Right
1st
2nd
2315
2827
Corticaldepth
AL PM
0
0.5
1
2435
2773
Corticaldepth
AL PM
0
0.5
1
2493
2762
Corticaldepth
AL PM
0
0.5
1
2543
2833
Corticaldepth
AL PM
0
0.5
1
T1 (ms)
S TAT I S T I C A L I N F E R E N C E
dIhemi = Ileft Iright dIorder = I1st I2nd
• Paired differences matching order or hemisphere
S TAT I S T I C A L I N F E R E N C E
dIhemi = Ileft Iright dIorder = I1st I2nd
dIorder = b0 +edIhemi = b0 +e
• Paired t-test (left vs. right; 1st vs. 2nd)
• Paired differences matching order or hemisphere
S TAT I S T I C A L I N F E R E N C E
dIhemi = Ileft Iright dIorder = I1st I2nd
dIorder = b0 +edIhemi = b0 +e
• Paired t-test (left vs. right; 1st vs. 2nd)
• Paired differences matching order or hemisphere
• Paired t-test covarying the other variables & interaction
dIhemi = b0 +b1 ⇥order+e dIorder = b0 +b1 ⇥hemi+e
S TAT I S T I C A L I N F E R E N C E
dIhemi = Ileft Iright dIorder = I1st I2nd
dIorder = b0 +edIhemi = b0 +e
• Paired t-test (left vs. right; 1st vs. 2nd)
• Paired differences matching order or hemisphere
• Paired t-test covarying the other variables & interaction
dIhemi = b0 +b1 ⇥order+e dIorder = b0 +b1 ⇥hemi+e
http://www.math.mcgill.ca/keith/surfstat/Worsely et al. (2009) NeuroImage
• RFT for multiple comparisons correction; FWHM= 2 pixels
Left - Right
L-R controlling
order
Effect of order
in L-R diff
1st - 2nd
1st-2nd covarying
hemisphere
Effect of hemi
in 1st-2nd diff
R E S U LT
• Greater T1 in the left HG

(Higher myelin in the right HG)
[1] Warrier et al., 2009, J Neurosci
R E S U LT
• Greater T1 in the left HG

(Higher myelin in the right HG)
• Lateralization of HG?
• Structural difference of HG between hemispheres
and specialized sensitivity to temporal/spectral
information [1]
[1] Warrier et al., 2009, J Neurosci
R E S U LT
• Greater T1 in the left HG

(Higher myelin in the right HG)
• Lateralization of HG?
• Structural difference of HG between hemispheres
and specialized sensitivity to temporal/spectral
information [1]
• The application is for demonstration of inter-structure
comparison of myelination profiles
[1] Warrier et al., 2009, J Neurosci
F U R T H E R A P P L I C AT I O N S
• Other regions: primary
somatosensory/motor areas
F U R T H E R A P P L I C AT I O N S
5 10 15 20
0
20
40
60
inx−coordinate
Order of eigenvector
5 10 15 20
0
2
4
6
8
iny−coordinate
Order of eigenvector
5 10 15 20
0
5
10
15
inz−coordinate
Order of eigenvector
data1
data2
data3
data4
data5
data6
Y(p) = q(p)+e(p),
q(p) =
k
Â
i=0
bjyj
ˆb = (y0
y) 1
y0
Y
[1] Kim et al. (2012) MMBIA
• Other regions: primary
somatosensory/motor areas
• Shape descriptor for group
differentiation (e.g. musicians):
Fourier coefficients [1] or the
eigenvalues of LB operator
T h i s w o r k i s f u n d e d b y t h e I n t e r n a t i o n a l M a x P l a n c k R e s e a rc h
S c h o o l o n N e u ro s c i e n c e o f C o m m u n i c a t i o n ( I M P R S - N e u ro c o m )
T H A N K Y O U F O R AT T E N T I O N !
© Hans-Joachim Krumnow

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Group-wise analysis on myelination profiles of cerebral cortex using the second eigenvector of Laplace-Beltrami operator

  • 1. G R O U P - W I S E A N A LY S I S O N M Y E L I N AT I O N P R O F I L E S O F C E R E B R A L C O R T E X U S I N G T H E S E C O N D E I G E N V E C T O R O F L A P L A C E - B E LT R A M I O P E R AT O R S E U N G - G O O K I M , J O H A N N E S S T E L Z E R , P I E R R E - L O U I S B A Z I N A D R I A N V I E H W E G E R , T H O M A S K N Ö S C H E ISBI 2014, 1st of May, Beijing, China
  • 2. O V E R V I E W • Aim: Intersubject correspondence for group-wise analysis on myelination profiles from the high-field MRI
  • 3. O V E R V I E W • Aim: Intersubject correspondence for group-wise analysis on myelination profiles from the high-field MRI • Method: Parametrization using the second Laplace- Beltrami eigenvector
  • 4. O V E R V I E W • Aim: Intersubject correspondence for group-wise analysis on myelination profiles from the high-field MRI • Method: Parametrization using the second Laplace- Beltrami eigenvector • Application: Statistical inference using random field theory on Heschl’s gyrus in auditory cortex
  • 5. M Y E L I N AT I O N P R O F I L E A N D I N - V I V O I M A G I N G I N T R O D U C T I O N & M O T I VA T I O N
  • 6. M Y E L O A R C H I T E C T U R E O F C O R T E X (cc) Quasar Jarosz
  • 7. Beck (1928) G M W M M Y E L O A R C H I T E C T U R E O F C O R T E X Nieuwenhuys (2013) Ed. Geyer & Turner (cc) Quasar Jarosz
  • 8. Vogt (1903) C Y T O - M Y E L O - Beck (1928) G M W M M Y E L O A R C H I T E C T U R E O F C O R T E X Nieuwenhuys (2013) Ed. Geyer & Turner (cc) Quasar Jarosz
  • 9. Vogt (1903) C Y T O - M Y E L O - Beck (1928) G M W M M Y E L O A R C H I T E C T U R E O F C O R T E X Nieuwenhuys (2013) Ed. Geyer & Turner (cc) Quasar Jarosz Hopf (1954)
  • 10. Vogt (1903) C Y T O - M Y E L O - Beck (1928) G M W M M Y E L O A R C H I T E C T U R E O F C O R T E X Nieuwenhuys (2013) Ed. Geyer & Turner (cc) Quasar Jarosz Hopf (1954)
  • 11. I N - V I V O I M A G I N G O F I N T R A C O R T I C A L M Y E L O A R C H I T E C T U R E U S I N G 7 T M R I • Quantitative T1 mapping (qT1) • T1 inversely correlates with myelination • Myelin is the main contribution to the T1 contrast [1] Geyer et al. (2011) Front Hum Neurosci ex-vivo in-vivo [1] Eickhoff et al. (2005) Hum Brain Mapp
  • 12. I N T E R S U B J E C T C O R R E S P O N D E N C E C S F G M W M
  • 13. I N T E R S U B J E C T C O R R E S P O N D E N C E C S F G M W M
  • 14. W H O L E B R A I N R E G I S T R AT I O N ? • Not yet fully developed for high-field MRIs • Signal loss in ventral regions • Different image contrast (quantitative T1 mapping) • Dimensionality from 
 sub-mm resolution
  • 15. M O T I VAT I O N : C O R R E S P O N D E N C E • To construct correspondence between myelination profiles in order to infer group-wise differences • Circumventing whole-brain registration issues • More precise than averaging within a ROI
  • 16. M O T I VAT I O N : C O R R E S P O N D E N C E • To construct correspondence between myelination profiles in order to infer group-wise differences • Circumventing whole-brain registration issues • More precise than averaging within a ROI • Parametrization using the second Laplace-Beltrami eigenvector Lévy (2006) SMI
  • 17. T H E S E C O N D L A P L A C E - B E LT R A M I E I G E N V E C T O R • Monotonous increase along the longest geodesic distance
  • 18. T H E S E C O N D L A P L A C E - B E LT R A M I E I G E N V E C T O R • Monotonous increase along the longest geodesic distance • Used to construct medial axes & Reeb graph for arbitrarily shaped structures Seo et al. (2011) SPIE Shi et al. (2008) MICCAIShi et al. (2008) IEEE CVPR Reuter et al. (2009) CAD
  • 19. A P P L I C AT I O N : H E S C H L’ S G Y R U S ( H G )
  • 20. A P P L I C AT I O N : H E S C H L’ S G Y R U S ( H G ) A I L P Wallace et al. (2002) Exp Brain Res A I L P S TA
  • 21. M Y E L I N AT I O N P R O F I L E E S T I M AT I O N P R E P R O C E S S I N G
  • 22. S U B J E C T S & I N - V I V O I M A G I N G • Six healthy participants: all male, age=25 ± 2 y.o. • MP2RAGE (magnetization-prepared rapid gradient echo with two inversion times) at 0.7 mm isovoxel using a 7 T scanner (Siemens) Marques et al. (2010) NeuroImage qT1T1w
  • 23. T1w at 1mm isovoxel
  • 24. T1w at 1mm isovoxel qT1 at 0.7 mm isovoxel
  • 25. T1w at 1mm isovoxel qT1 at 0.7 mm isovoxel Regenerated surfaces
  • 26. M A N U A L D E L I N E AT I O N O F H G • Duplication/sulcus (10) • Single HG (LH:1, RH:1)
  • 27. R E A L I S T I C C O R T I C A L L AY E R I N G [ 1 ] [1] Waehnert et al. (2013) NeuroImage
  • 28. R E A L I S T I C C O R T I C A L L AY E R I N G [ 1 ] http://www.cbs.mpg.de/institute/software/cbs-hrt[1] Waehnert et al. (2013) NeuroImage
  • 29. T H E S E C O N D L A P L A C E - B E LT R A M I E I G E N V E C T O R PA R A M E T E R I Z A T I O N & I N F E R E N C E
  • 30. • Laplace-Beltrami (LB) operator 𝚫 of function 𝒇 defined on an arbitrary manifold is given by: L A P L A C E - B E LT R A M I E I G E N V E C T O R S D f := div(grad f) M 2 R2 ⇢ R3
  • 31. • To find eigenvector Ѱj and eigenvalue 𝝀j of LB, solve: 0 = l0 < l1  l2  ··· y0,y1,y2 ··· • Laplace-Beltrami (LB) operator 𝚫 of function 𝒇 defined on an arbitrary manifold is given by: L A P L A C E - B E LT R A M I E I G E N V E C T O R S D f := div(grad f) M 2 R2 ⇢ R3 Dyj = ljyj
  • 32. • To find eigenvector Ѱj and eigenvalue 𝝀j of LB, solve: 0 = l0 < l1  l2  ··· y0,y1,y2 ··· • Laplace-Beltrami (LB) operator 𝚫 of function 𝒇 defined on an arbitrary manifold is given by: L A P L A C E - B E LT R A M I E I G E N V E C T O R S D f := div(grad f) [1] Qui et al., (2006) TMI; [2] Aubry et al. (2011) ICCV CY = lAY C Cotagent matrix A Mass matrix • Discretization of LB using FEM, then the eigenvectors can be computed from generalized eigenvalue problem [1,2]: M 2 R2 ⇢ R3 Dyj = ljyj
  • 33. • To find eigenvector Ѱj and eigenvalue 𝝀j of LB, solve: 0 = l0 < l1  l2  ··· y0,y1,y2 ··· • Laplace-Beltrami (LB) operator 𝚫 of function 𝒇 defined on an arbitrary manifold is given by: L A P L A C E - B E LT R A M I E I G E N V E C T O R S D f := div(grad f) [1] Qui et al., (2006) TMI; [2] Aubry et al. (2011) ICCV CY = lAY C Cotagent matrix A Mass matrix • Discretization of LB using FEM, then the eigenvectors can be computed from generalized eigenvalue problem [1,2]: http://www.di.ens.fr/~aubry/wks.html *smoothed for visualization M 2 R2 ⇢ R3 Dyj = ljyj
  • 34. L E V E L S E T S B A S E D O N L B 2
  • 35. PA R A M E T E R I Z E D M Y E L I N P R O F I L E S C S F G M W M
  • 36. AV E R A G E D M Y E L I N I M A G E S Left Right 1st 2nd 2315 2827 Corticaldepth AL PM 0 0.5 1 2435 2773 Corticaldepth AL PM 0 0.5 1 2493 2762 Corticaldepth AL PM 0 0.5 1 2543 2833 Corticaldepth AL PM 0 0.5 1 T1 (ms)
  • 37. AV E R A G E D M Y E L I N I M A G E S Left Right 1st 2nd 2315 2827 Corticaldepth AL PM 0 0.5 1 2435 2773 Corticaldepth AL PM 0 0.5 1 2493 2762 Corticaldepth AL PM 0 0.5 1 2543 2833 Corticaldepth AL PM 0 0.5 1 T1 (ms)
  • 38. S TAT I S T I C A L I N F E R E N C E dIhemi = Ileft Iright dIorder = I1st I2nd • Paired differences matching order or hemisphere
  • 39. S TAT I S T I C A L I N F E R E N C E dIhemi = Ileft Iright dIorder = I1st I2nd dIorder = b0 +edIhemi = b0 +e • Paired t-test (left vs. right; 1st vs. 2nd) • Paired differences matching order or hemisphere
  • 40. S TAT I S T I C A L I N F E R E N C E dIhemi = Ileft Iright dIorder = I1st I2nd dIorder = b0 +edIhemi = b0 +e • Paired t-test (left vs. right; 1st vs. 2nd) • Paired differences matching order or hemisphere • Paired t-test covarying the other variables & interaction dIhemi = b0 +b1 ⇥order+e dIorder = b0 +b1 ⇥hemi+e
  • 41. S TAT I S T I C A L I N F E R E N C E dIhemi = Ileft Iright dIorder = I1st I2nd dIorder = b0 +edIhemi = b0 +e • Paired t-test (left vs. right; 1st vs. 2nd) • Paired differences matching order or hemisphere • Paired t-test covarying the other variables & interaction dIhemi = b0 +b1 ⇥order+e dIorder = b0 +b1 ⇥hemi+e http://www.math.mcgill.ca/keith/surfstat/Worsely et al. (2009) NeuroImage • RFT for multiple comparisons correction; FWHM= 2 pixels
  • 42. Left - Right L-R controlling order Effect of order in L-R diff 1st - 2nd 1st-2nd covarying hemisphere Effect of hemi in 1st-2nd diff
  • 43. R E S U LT • Greater T1 in the left HG
 (Higher myelin in the right HG) [1] Warrier et al., 2009, J Neurosci
  • 44. R E S U LT • Greater T1 in the left HG
 (Higher myelin in the right HG) • Lateralization of HG? • Structural difference of HG between hemispheres and specialized sensitivity to temporal/spectral information [1] [1] Warrier et al., 2009, J Neurosci
  • 45. R E S U LT • Greater T1 in the left HG
 (Higher myelin in the right HG) • Lateralization of HG? • Structural difference of HG between hemispheres and specialized sensitivity to temporal/spectral information [1] • The application is for demonstration of inter-structure comparison of myelination profiles [1] Warrier et al., 2009, J Neurosci
  • 46. F U R T H E R A P P L I C AT I O N S • Other regions: primary somatosensory/motor areas
  • 47. F U R T H E R A P P L I C AT I O N S 5 10 15 20 0 20 40 60 inx−coordinate Order of eigenvector 5 10 15 20 0 2 4 6 8 iny−coordinate Order of eigenvector 5 10 15 20 0 5 10 15 inz−coordinate Order of eigenvector data1 data2 data3 data4 data5 data6 Y(p) = q(p)+e(p), q(p) = k  i=0 bjyj ˆb = (y0 y) 1 y0 Y [1] Kim et al. (2012) MMBIA • Other regions: primary somatosensory/motor areas • Shape descriptor for group differentiation (e.g. musicians): Fourier coefficients [1] or the eigenvalues of LB operator
  • 48. T h i s w o r k i s f u n d e d b y t h e I n t e r n a t i o n a l M a x P l a n c k R e s e a rc h S c h o o l o n N e u ro s c i e n c e o f C o m m u n i c a t i o n ( I M P R S - N e u ro c o m ) T H A N K Y O U F O R AT T E N T I O N ! © Hans-Joachim Krumnow