1. Advanced
MR
Imaging
in
Epilepsy
Dr.
Vincent
Lai
MBChB,
FRCR(UK),
FHKCR,
FHKAM(Radiology)
Consultant
Radiologist,
Hong
Kong
BapBst
Hospital
Honorary
Clinical
Assistant
Professor,
University
of
Hong
Kong

2. Overview
General
imaging
findings
&
concept
Various
funcBonal
imaging
techniques
Our
preliminary
work

3. Introduc:on
• Very
heterogeneous
imaging
spectrum
• IdenBficaBon
of
epileptogenic
lesion
is
crucial
in
achieving
seizure
free
outcome
aPer
surgery

4. E:ologies
of
Epilepsy
MalformaBon
of
corBcal
development
Focal
corBcal
dysplasia
Heterotopia
Polymicrogyria
Mesial
temporal
sclerosis
Tumor
DysembryoplasBc
neuroepithelial
tumor
Ganglioglioma
Astrocytoma
Oligodendroglioma
Cavernoma
Vascular
cerebral
insult
Chronic
corBcal/subcorBcal
infarct
Arteriovenous
malformaBon
Amyloid
angiopathy
Nonvascular
cerebral
insult
Post-­‐traumaBc
PostoperaBve
PostencephaliBs
Postanoxia
Others
Abnormal
venous
drainage
Arachnoid
cyst/
neuroepithelial
cyst
Focal
calcificaBon/
corBcal
atrophy

5. Goal
of
Epilepsy
Imaging
Detec:on
of
epileptogenic
lesion
Localiza:on
of
epileptogenic
lesion
TriangularizaBon
amongst
Seizure
emiology,
EEG
&
Imaging

6. Current
MR
Imaging
Considera:on
High
resoluBon
structural
imaging
3D
MPRAGE/SPGR
T1W,
Oblique
Coronal/3D
T2W
&
FLAIR
T2W
SuscepBbility
weighted
imaging
FuncBonal
imaging
Radionuclide,
T2
relaxometry,
MRS,
Diffusion,
ASL,
MR
volumetry

7. Are
we
doing
well?
ProblemaBc
issue
in
MR-­‐negaBve
paBents
Does
this
really
exist?

8. Where
are
we
upto
?
• 2/3
of
MR
negaBve
paBents
have
idenBfiable
lesion
(oOen
subtle
MCD)
on
3.0
T
– Temporal
50%
– Frontal
40%
– Majority
is
FCD
Knake
S
et
al.
2005
Neurology
• 65%
of
drug
resistant
epilepsy
has
idenBfiable
lesion
– Frequently
MTS
Vezina
LG
2011
Epilepsia

9. M/
22
yrs
old
LeO
hippocampal
FCD

10. Taylor’s
FCD
with
balloon
cells,
radial
band
Colombo
N
et
al.
2003
AJNR

11. F/4.5
yrs
old
Right
insular
FCD

12. Malforma:on
of
Cor:cal
Development

13. Polymicrogyria
Agyria
Grant PE et al. 1997 AJNR

14. TPO
Syndrome/
Posterior
Quadran:c
Cor:cal
Dysplasia

15. Low
Grade
Astrocytoma

16. MTS

17. Parahippocampus
Forms
mesial
&
inferior
gyrus
of
temporal
lobe
Includes:
Entorhinal
&
perirhinal
corBces
Parahippocampal
cortex
Contributes
to:
Seizure
iniBaBon
epileptogenesis

18. Parahippocampal
epilepsy
A
subset
of
MTLE
A
cause
of
MR-­‐negaBve
MTLE
T2W
hyperintense
signal
in
parahippocmapal
WM
Blurring
of
GW
juncBon
Normal
corBcal
thickness
Pillay
N
er
al.
2009
Epilepsia

19. Challenging
Issue
GeneBc
Disrup:on
of
normal
cor:cal
development
Early
environmental
factors
Microdysgenesis
of
neocortex
or
subtle
MCD
Majority
of
MR-­‐nega:ve
PET-­‐posi:ve
cases
Mild MCD (I & II) in 12-40%: Carne RP et al. 2004 Brain; Huba R et al. 2012 Epliepsy & Behavior

20. So,
how
can
we
do
it?

21. Radionuclide
Imaging
PET
vs
SPECT
Noninvasive
Presurgical
mapping
Uses:
• MR-­‐negaBve
• Several
lesions
• Discordant
findings
between
EEG
&
structural
imaging

22. Advanced
MR
Imaging
Techniques
T2
Relaoxmetry
MR
Volumetry
MR
Spectroscopy
Diffusion
Tensor
Imaging
Arterial
Spin
labeling

23. T2
Relaxometry
T2
relaxaBon
Bme
↑
in
the
epilepBc
focus
Woermann
et
al.
1998;
Namer
et
al.
1998;
Van
Paesschen
et
al.
1995;
Jackson
et
al.
1993)
SuggesBon
of
superior
detecBon
rate
as
compared
with
volumetry
Bernasconi
A
et
al.
2000
Neuroimage
But
not
confirmed
in
later
and
recent
study
with
more
advanced
MR
volumetry:
– Improved
detec_on
rate
in
19%
of
pa_ents
only
Coan
AC
et
al.
2013;
AJNR

24. T2
Relaxometry
False
+ve
in
upto
50%
of
visually
detected
T2
signal
changes
in
hippocampus
Voxel
based
quan:ta:ve
analysis
is
more
reliable
Sumar I et al. 2011; Epilepsy research

25. MR
Volumetry
i.
Segmenta_ons
by
VBM
ii. Orienta_on-­‐corrected,
spaBally
normalized,
Bssue
classified
iii. Par__on
the
whole-­‐brain
to
GM,
WM
and
iv.
FIRST:
fieng
a
mesh
to
the
surface
of
the
amygdala
&
hippocampus

26. Manual
vs
automated
segmenta:on
In
a
study
of
46
paBent
Manual
method
vs
various
automated
methods
LocalInfo
>
HAMMER
>
FreeSurfer
LateralizaBon
accuracy:
Manual
(78%)
Automated
(74%)
Akhondi-Asl A et al. 2011 Neuroimage

27. Quan:ta:ve
MR
volumetry
in
hippocampal
atrophy
Automated
MR
volumetry
Hippocampal
asymmetry
(pa_ents
&
normal)
High
discriminaBng
power
Sensi_vity
89.5%;
Specificity
94.1%
LateralizaBon
accuracy:
88%
(visual
inspec_on:
76-­‐85%)
Farid N et al. 2012 Radiology

28. ?
Performance
in
3T
In
a
study
of
203
paBents
with
hippocampal
sclerosis…
Help
↑
detec:on
rate
in
28%
of
pa:ents
with
hippocampal
sclerosis
Coan AC et al. 2013 AJNR

29. Pialls
reflects
a
combinaBon
of
cor:cal
thickness
&
surface
area
measurements

30. Morphological
analysis
Average
convexity
(Fischl
et
al.
1999)
Sharpness/
Curvedness/
Folding
index
(Pienaar
et
al.
2008)
GyrificaBon
index
(Schaer
et
al.
2008)
Sulcal
paiern
(Kim
et
al.
2008)
Shape
parameter
-­‐
Jacobian
matrix
(Ronan
et
al.
2011)
Surface
area/geometric
distorBon
(Alhusaini
et
al.
2012)
Reflects changes in underlying connectivity and white matter tracts

31. So,
they
advocate…
Surface-­‐based
MRI
morphometry
post-­‐processing
surface
reconstruc_on
morphometric
measures
lesion
tracing
Sn
92%,
Sp
96%
Thesen T et al. 2011 Open Access

32. MR
Spectroscopy

33. MRS
–
General
Principles
Molecules/
Metabolites
Func:on/
Clinical
relevance
NAA
Marker
of
neuronal
density
&
viability
Cr
Marker
for
energy–dependent
system
Cho
Marker
of
increased
inflammatory/glioBc
process
&
pathological
changes
in
membrane
turnover
Lactate
Elevated
aPer
seizure
&
in
hypoxia/ischemic
injury
Mitochondral
disorder
Glutamate
Major
excitatory
neurotransmiier,
toxic
if
elevated
leading
to
neuronal
death
ml
Marker
of
gliosis

34. Short
TE
(35
ms)
Long
TE
(144
ms)
Very
Long
TE
(288
ms)
Typical
Spectra

35. Single
vs
Mul:-­‐voxel
Spectroscopy
Single-­‐voxel
Higher
SNR
Short
acquisiBon
Bme
(~3
mins)
Metabolic
disease
1. 1
voxel
at
BG
2. 3
voxels
at
CS,
LN,
OP
cortex
Temporal
lobe
epilepsy
2
voxels
at
bilateral
hippocampi
Mul:-­‐voxel
Larger
volume
of
informaBon
Long
acquisiBon
Bme
(~8
mins)
Allow
3D
acquisiBon

36. Technical
Considera:ons
• Higher
magneBc
field
strength
(higher
SNR)
• MulBchannel
(32-­‐channel)
receiver
coils
(higher
SNR)
Keil
B
et
al.
2012
Magn
Reson
Med
• Shimming
(maximise
B0
homogeneity)
Kanayanma
S
et
al.
1996
Magn
Reson
Med;
Hetherington
HP
et
al.
2006
Magn
Reson
Med
• Fast
spiral
acquisiBon
(allow
fast
spa_al
encoding)
Andronesi
OC
et
al.
2012
Radiology
• AdiabaBc
pulses
(compensate
for
radiofrequency
inhomgeneity)
Garwood
M
et
al.
1989
Magn
Reson
Med;
Andronesi
OC
et
al.
2010
J
Magn
Reson

37. Role
of
MRS
Screening
of
metabolic
derangement
Adjuvant
in
evaluaBon
of
medically
refractory
TLE
CharacterizaBon
of
lesions/
masses
?Localizing
techniques
in
extratemporal
epilepsy

38. MRS
Screening
of
metabolic
derangement
Mitochondrial
disorders
↓ Cho
in
normal
appearing
cerebellar
WM
(80%)
peritrigonal
WM
(67%)
corBcal
GM
(60%)
↓ NAA/Cr
in
normal
appearing
cerebellum
(93%)
cortex
(87%)
↑
Amino
acids
&
Lactate
Bianchi C et al. 2003 AJNR

39. MRS
Screening
of
metabolic
derangement
EnzymaBc
disorders
Cr
deficiency
Prevalence:
0.25%
Inherited
enzymaBc
defects:
AGAT
GAMT
SLC6A8
↓ Cr
in
normal
brain
Arias A et al. 2007 Clin Biochem

40. MRS
Adjuvant
in
evaluaBon
of
medically
refractory
TLE
TLE
↓ NAA
↓
NAA/Cr
raBo
86%
agreement
with
EEG
(c.f.
83%
for
volumetry
with
EEG)
12%
in
MR-­‐negaBve
TLE
Cendes F et al. 1997 Ann Neurol; Kuzniecky R et al. 1998 Neurology

41. MRS
CharacterizaBon
of
lesions/
masses
FCD vs
Neoplasm
FCD
↓ NAA/Cr
raBo
↑ GABA,
akanine,
tyrosine,
lactate,
inositol
No
elevaBon
in
Cho/NAA
Pathology:
type
IIB
FCD
Caruso PA et al. 2013 Neuroimag Clin N Am

42. MRS
CharacterizaBon
of
lesions/
masses
FCD
vs
Neoplasm
Astrocytoma
↓ NAA,
↑
Cho
↑
Cho/NAA
,
↓
NAA/Cr raBos
Pathology:
Angiocentric
astrocytoma
Caruso PA et al. 2013 Neuroimag Clin N Am

43. MRS
LocalizaBon
in
nonlesional
epilepsy
FCD
Using
MVS
&
subdural
electrodes
Areas
of
↑
Cho/NAA
&
↓
NAA/Cr
raBos
overlapped
with
ictal
zones
Krsek P et al. 2007 Eur Radiol

44. Diffusion
Tensor
Imaging

45. DTI
–
General
Principle
Measurement
of:
Magnitude
&
Direc:on
Of
water
diffusion
Indirect
evalua:on
of
integrity
of
axonal
microenvironment
anisotropic

46. Quan:fica:on
Frac:onal
Anisotropy
(FA)
Normal
fiber
tracts:
Ranges
from
0
–
1
Anisotropic
(high
FA)
0:
isotropic
diffusion
1:
anisotropic
diffusion
Degenerated
fiber
tracts:
MD
λ1,
λ2,
λ3
↓ FA
Wallerian
degenera_on
Demyelina_on/
dysmyelina_on
Maldevelopment

47. FCD
Significant
reducBon
of
FA
in
underlying
subcorBcal
WM
HypomyelinaBon
?
SeneiBvity
Technical consideration: Tesla; no of gradient…
Gross DW et al. 2005 Can J Neurol Sci

48. MTLE
Widespread
WM
changes
↓ FA
values
PosiBve
correlaBon
with
hippocampal
volume
Scanlon C et al. 2013 J Neurol; Oquz KK et al. 2013; AJNR

49. Arterial
Spin
Labeling
Noninvasive
EvaluaBon
of
CBF
Interictal
–
hypoperfused;
Ictal
-­‐
hyperperfused
Wolf et al. 2001 AJNR; Madan N et al. 2009 Epilepsia

50. Correla:on
with
Radionuclide
Imaging
15
children
18F-­‐FDG
PET
and
DTI
MRI
Hypometabolism
correlates
with
DTI
indices
MR+ve
&
MR-­‐ve
pa_ents
Lippe S et al. 2012 Epileptic disord

51. Our
Preliminary
Work…

52. T1
rho
MR
Imaging
Provides
informaBon
on
slow
molecular
moBon
–
–
–
–
Transverse
magneBzaBon
of
T1
is
“locked”
by
spin-­‐lock
frequency
Made
to
decay
slower
Followed
by
convenBonal
imaging
GeneraBon
of
T1rho
map
In
neuroimaging,
has
been
uBlized
in:
– Brain
tumors
– AD
and
Parkinson’s
disease

53. Hypothesis
&
Aim
Hypothesis:
T1
rho
imaging
is
able
to
reflect
early
neuronal
loss
in
the
epileptogenic
zone
Aim:
Determine
the
feasibility
of
noninvasive
T1
rho
MR
imaging
in
idenBficaBon
&
lateralizaBon
of
epileptogenic
zone

54. Inclusion
criteria
MR-­‐posi:ve
i) PaBents
with
established
MTL
epilepsy
by
EEG,
MTL
epilepsy
seizure
semiology
and
MR
proven
MTS
ii) Unilateral
disease
iii) No
history
of
epilepsy
surgery
iv) No
other
epileptogenic
focus
Normal
subjects
i) No
known
epilepsy
or
any
structural
lesion
idenBfied
on
MR
brain
imaging
ii) No
history
of
cerebral
disease
iii) No
history
of
brain
surgery
Included:
15
normal
subjects;
7
pa_ents
2
pa_ents
excluded
(significant
mo_on
ar_facts
&
bilateral
MTS)

55. Scanning
parameters
3.0
Tesla
MR
scanner,
uBlizing
a
8-­‐channel
head
coil.
T2
relaxometry:
•
Sequence:
TSE;
TR/TE
(ms):
1868/20;
FOV(mm):
240*240;
Matrix:
268*268;
Slice
thickness:
3
mm;
Gap:
0;
Scan
Bme:
6
min
42
sec.
T1rho:
•
Sequence:
B-­‐TFE;
FOV(mm):
240*240;
Matrix:
160
160;
During
of
spin-­‐lock
pulse
(ms):
1,
10,
20,
30,
40;
Spin-­‐lock
frequency:
500
Hz;
TI
(ms):
860;
Slice
thickness:
3
mm;
Bandwidth:
130
Hz/pixel;
Echo
train
length:
4;
Scan
Bme:
9
min
10
sec.
3D
T1-­‐weighted
MPRAGE:
•
Sequence:
MPRAGE;
TR/TE:
7.0/3.1
msec;
Flip
angle:
8;
FOV
(mm):
250*250;
Matrix:
256*256;
Slice
thickness:
1
mm;
Gap:
0.

56. ROIs
defini:on
–
on
T2W
Manual
drawing
of
ROI
to
contour:
Amygdala
Hippocampal
head
Hippocampal
body
Hippocampal
tail
Verified
against
automated
ROIs
-­‐comparable
results
-­‐
no
significant
differences
Manual
ROI
is
accurate

57. ROIs
Coregistra:on
T2W
T2
Relaxometry
To
obtain
the
mean
values
&
SD
of:
-­‐T1
rho
value
-­‐T2
relaxaBon
Bme
T1rho
Asymmetric
RaBo

58. Sta:s:cal
Analysis
• Gaussian
distribuBon
and
homogeneity
tests
• Paired
t-­‐test
between
leP
and
right
side
for
each
group
• StandardizaBon
of
T2
relaxometry
and
T1rho
values
according
to
the
corresponding
values
of
the
normal
control
group
through
Z-­‐score
transformaBon:
z
=
(X
-­‐
μ)
/
σ
• Abnormal
if:
>2
SD
away
from
the
mean
of
the
normal
group:
z
>
2
or
z
<
-­‐2
p<0.05
will
be
considered
as
sta_s_cal
significant.

59. Results
–
Normal
Subjects
(mean±SD)
Asymmetric
Ra:o
SD
95.1.
±
3.12
96.20
±
3.14
0.9863
0.0122
Hippo
Head
96.51
±
3.31
97.12
±
3.49
0.9841
0.0210
Hippo
Body
90.79
±
4.72
91.27
±
3.92
0.9876
0.0085
Hippo
Tail
86.69
±
6.33
87.83
±
5.59
0.9849
0.0124
Amygdala
144.89
±
35.22
144.74
±
36.39
0.9888
0.0073
Hippo
Head
140.26
±
35.56
139.69
±
36.27
0.9896
0.0076
Hippo
Body
133.58
±
34.55
134.12
±
33.75
0.9888
0.0085
Hippo
Tail
133.97
±
34.8
134.49
±
34.61
0.9880
0.0060
Right
Lek
(mean±SD)
Amygdala
T2
relaxometry
T1
rho
Note:
Asymmetry
=
Min(L,
R)
/
Max(L,
R)
SD
=
standard
deviaBon
The
respec_ve
asymmetric
ra_o
were
then
used
as
reference
for
comparison
in
pa_ents’
group
mean
+/-­‐
2SD

60. Parametric
Maps
of
Normal
Subject

61. F/22
yrs
old;
Lek
MTS

62. M/
45
yrs
old;
Lek
MTS

64. Accuracy
of
T2
relaxometry
&
T1
rho
results
Comparison
against
Volumetry
IYY
T2R
y
NKY
Amyg
T1rho
Volume
y
y
y
y
Hipp
Head
T2R
T1rho
Volume
y
y
y
y
y
y
y
y
y
y
y
Y
y
y
y
y
y
y
y
y
y
y
WYY
y
CYY
y
CHY
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
y
Y
FKY
CYSA
y
y
y
y
y
T2R
Hipp
Tail
T1rho
Volume
y
y
Hipp
Body
T2R
T1rho
Volume
y
T2
relaxometry:
Sn
=
60.9%
(14/23);
Sp
=
100.0%
(4/4)
T1rho:
Sn
=
100.0%
(24/24);
Sp
=
50.0%
(2/42)

65. Distribu:on
of
Asymmetric
Ra:os

66. F/7
yrs
old;
GTC
seizure;
MR-­‐ve
Potential role in detecting WM changes

67. Limita:ons/
Improving
work
Recruit
more
subjects
(paBents
and
normal)
to
further
validate
diagnos_c
value
of
T1rho
Lack
of
histopathological
correlaBon
Perform
DTI
analysis
to
test
the
feasibility
in
detec_ng
WM
changes
Plane
of
imaging
-­‐
coronal
3D
whole
brain
imaging
techniques
Use
of
longer
spin
lock
Bmes

68. T1
rho
MR
Imaging
• Feasible
in
idenBficaBon
of
epileptogenic
zone
• A
sensi:ve
marker
more
sensi_ve
than
T2
relaxometry
more
sensi_ve
than
volumetry
• Can
potenBally
detect
early
molecular
changes

69. Conclusion
• Wide
variety
of
eBologies
MCD,
MTS
• Concept
of
MR-­‐negaBve
epilepsy
Does
it
really
exist?
• Availability
of
various
advanced
MR
imaging
techniques
+
limitaBon
Feasibility
in
clinical
prac_se?
• Promising
result
of
T1rho
imaging
Thank you