XIX SYMPOSIUM NEURORADIOLOGICUM
BOLOGNA, Oct 4-9.2010
MULTIMODALITY APPROACH TO IMAGING
IN DEMENTIA ROLE OF MR AND CT PERFUSION AND DTI
Marek J. SASIADEK
Anna ZIMNY
Pawel SZEWCZYK
Department of General and Interventional Radiology and
Neuroradiology, Wrocław Medical University, Poland
BACKGROUND
Modern CT and MR techniques, like
- CT volumetry
- CT perfusion (pCT)
- MR perfusion (PWI)
- diffusion tensor imaging (DTI)
- MR spectroscopy (MRS)
- voxel based morphometry (VBM)
- functional magnetic resonance imaging (fMRI)
play a growing role in diagnostics of dementia
BACKGROUND
The following methods will be discussed:
CT perfusion (pCT)
MR perfusion (PWI)
diffusion tensor imaging (DTI)
The value of these imaging methods in diagnostics
of dementia has not been established yet
CT and MR perfusion
• Evaluation of cerebral microcirculation (perfusion)
• Main parameters:
- CBV (cerebral blood volume)
- CBF (cerebral blood flow)
- MTT (mean transit time)
- TTP (time to peak)
CT and MR perfusion
Dementia = hipoperfusion
Vascular hipothesis of Alzheimer’s disease
Hipoperfusion of gray matter
secondary
degenerative changes
formation of
amyloid plaques
CBV
CBF
MTT
Vascular changes in AD
• aberrant angiogenesis
• small vessel degeneration
• faulty blood-brain barrier
• atherosclerosis
neurovascular uncoupling
brain hypoperfusion
amyloid beta accumulation
CT perfusion - method
Multidetector CT unit
Slab – 1, 2, 4, 8,... cm
Contrast medium 40-50 ml i.v.,
4-5 ml/s
Delay ca 7 s
40- 50 scans 1 scan/s
Regions of interest
(ROIs)
CT perfusion– perfusion maps
Alzheimer’s disease
CBF
CBV
MTT
Own results – differentiation of dementia
ANOVA, LSD Tukey’s test (p <0,05)
Parametr
ADvsMD
ADvsVaD
CBF
0
CBV
0
17
18
MTT
0
0
MDvsVaD
ADvsGK
MDvsGK
VaDvsGK
9
9
11
11
2
0
9
9
0
0
3
0
10
10
99
66
Own results – severity of dementia
Pearson’s correlation coefficient (p <0,05)
Parametr
N=85
AD
MD
VaD
CBF
17
12
0
0
CBV
22
18
0
0
MTT
0
0
0
0
Frontal and temporal
gray matter regions
MR perfusion (PWI) – methods
• DSC – dynamic susceptibility contrast enhanced
imaging (perfusion dependent of the change of
magnetic susceptibility)
• DCE – dynamic contrast enhanced imaging
based on gradient T1-weighted images
• ASL – arterial spin labeling (labeled spins in
vascular bed) – quantitative rCBF evaluation
DSC in dementia
• Relative measurements of CBV to cerebellum
↓↓ rCBV temporoparietal regions (AD, MCI)
↓ rCBV sensory/motorical cortex (AD, MCI)
↓ rCBV hippocampi (AD, MCI)
Bozzao A et al , AJNR 2001
ASL in dementia
Hipoperfusion:
AD - parietal regions,
- cingulate gyrus
Frontal regions
MCI
- lower part of parietal lobes
Johnson NA et al. Pattern of Cerebral Hypoperfusion in Alzheimer Disease and
Mild Cognitive Impairment Measured with Arterial Spin-labeling MR Imaging:
Initial Experience. RSNA 2005; 234:851-859.
PWI - own protocol
• 1.5 T MR unit (GE Signa Hdx)
• 16-channel HNS coil
• PWI – dynamic susceptibility contrast (DSC)
EPI T2*-sequence
(TR 1.900 ms, TE 80 ms, FA 90◦, FOV 30 cm, matrix
192 x 128, NEX 1), 13 slices 8mm, gap 0, TA 1 min
26 s
• Contrast medium (Gadovist)– i.v. 0.3 mMol/kg, 5
ml/s + 20 ml of saline
PWI -
OWN PROTOCOL
Frontal regions
Hippocampi
Temporoparietal cortex
Posterior cingulum
rCBV
(related to cerebellum)
Own results
Cortex
Mean rCBV (SD)
ANOVA
AD
MCI
CG
Right
0.92
0.91
0.93
hippocampal
(0.12)
(0.2)
(0.08)
Left
0.92
0.93
0.94
hippocampal
(0.12)
(0.08)
(0.09)
Right
1.04
1.09
1.14
temporoparietal
(0.11)
(0.08)
(0.08)
Left
1.05
1.11
1.14
temporoparietal
Right
(0.12)
(0.09)
(0.06)
1.05
1.06
1.13
frontal
(0.16)
(0.08)
(0.09)
Left
1.03
1.05
1.13
frontal
(0.14)
(0.08)
(0.08)
Posterior
1.08
1.21
1.28
cingulate
(0.12)
(0.08)
(0.08)
regions
Post hoc Tukey LSD test, p values
AD vs CG
AD vs MCI
MCI vs CG
0.88
0.93
0.67
0.67
0.83
0.59
0.65
0.89
0.003*
0.001*
0.04*
0.13
0.01*
0.007*
0.03*
0.45
0.13
0.05
0.4
0.1
0.02*
0.005*
0.4
0.04*
< 0.0001*
< 0.0001*
0.0001*
0.04*
p values
Own results - AD vs control group
AD
rH
lH
rTP
CG
lTP
rF
lF
PC
G
both temporoparietal cortices (p=0.001, p=0.007)
left frontal cortex
(p=0.005)
PCG region
(p< 0.0001)
Own results - AD vs MCI
AD
rH
lH
MCI
rTP
lTP
rF
lF
PC
G
both temporoparietal cortices (p=0.04, p=0.03)
PCG region
(p=0.0001)
Own results - MCI vs control group
MCI
rH
lH
CG
rTP
lTP
rF
Left frontal cortex
PCG region
lF
PC
G
(p=0.04)
(p=0.04)
Diffusion tensor imaging (DTI)
Evaluation of visualization and integrity of the
white matter tracts
(preferable direction of diffusion according to the fibers’ course)
Fractional anisotropy (FA) map
tractography
DTI in dementia
neuron damage of cerebral cortex
secondary damage to the white matter (Wallerian
degeneration)
FA – fractional anisotropy
Dementia ↓ FA
DTI in dementia
↓ FA
• AD –temporal, parietal and frontal white matter
MCI – temporal white matter
(Huang J et al. AJNR 2007)
• AD – fronto-occipital fascicles, uncinate fascicles, cingulum, body of
corpus callosum
• MCI – cingulum
(Taoka et al. AJNR 2006, Zhang Y et al. Neurology 2009)
• DLB – parietal and occipital white matter, corpus callosum
(Bozzali M et al. Proc. Intl. Soc. Mag. Reson. Med. 2004)
• FTD – upper and lower longutudinal fascicles
(Matsuo K et al. Neuroradiology 2008)
DTI in dementia
Vascular dementia (VaD)
FA=0.425
FA=0.103
OWN PROTOCOL
•
•
•
•
•
•
-
DTI
EPI-DTI (TR=8500ms, TE=100ms)
FOV 240x240mm, matrix 128x128
Slices 4mm, gap 0mm, parallel to intercallosal line
25 directions, NEX=2
b value 0 i 1000s/mm2
TA 7min 29s
middle cerebellar peduncles
(MCP)
Projection tracts
Posterior limbs
of internal capsules
Callosal tracts
Genu and splenium
of corpus callosum
Association tracts
Superior
longitudinal
fascicles (SLF)
Inferior longitudinal
fascicles (ILF)
Association tracts
Fronto-occipital fascicles (IFOF)
cingulum
DTI – own results
White
matter tracts
Callosal
tracts
Association
tracts
Mean FA (SD)
ANOVA
Post hoc Tukey LSD test, p
values
p values
AD vs CG AD vs
MCI vs
MCI
CG
0.01
0.01
0.008
0.92
AD
MCI
CG
GCC
0.737
0.782
0.784
SCC
(0.07)
0.796
(0.06)
0.821
(0.05)
0.848
0.03
0.01
0.15
0.2
Left
(0.06)
0.578
(0.08)
0.594
(0.05)
0.629
0.01
0.001
0.2
0.03
SLF
Right
(0.05)
(0.05)
(0.04)
0.549
0.567
0.616
< 0.0001
< 0.0001
0.15
0.001
ILF
Left
(0.05)
(0.03)
(0.05)
0.564
0.560
0.613
0.001
0.0008
0.72
0.0007
ILF
Right
(0.05)
(0.05)
(0.04)
0.548
0.579
0.602
0.003
0.001
0.02
0.13
IFOF
Left
(0.05)
(0.05)
(0.05)
0.545
0.577
0.587
0.01
0.007
0.02
0.53
IFOF
(0.05)
(0.05)
(0.05)
Significant results (p < 0.05)
DTI- own results – association tracts
posterior cingulum
White
Mean FA (SD)
matter tracts
ANOVA
AD
MCI
CG
Right
0.550
0.605
0.660
PC
Left
(0.06)
(0.06)
(0.05)
0.596
0.618
0.686
PC
(0.05)
(0.05)
(0.04)
< 0.0001
Post hoc Tukey LSD test, p
values
AD vs CG
AD vs
MCI vs
MCI
CG
< 0.0001
0.0007
0.006
< 0.0001
< 0.0001
p values
right PC
0.0004
< 0.0001
left PC
0,8
0,8
0,7
0,7
0,6
0,6
0,5
0,5
0,4
0,4
0,3
0,3
0,2
0,2
0,1
0,1
0
0
AD
MCI
CG
AD
MCI
CG
MRS vs DTI vs PWI –
own results
Posterior
cingulum
AD
MCI
CG
1.37
1.51
1.50
< 0.0001*
(0.11)
(0.08)
(0.06)
Cho/Cr
0.60
0.60
0.59
0.81
0.52
0.73
0.74
mI/Cr
(0.06)
0.66
(0.07)
0.58
(0.04)
0.62
0.003*
0.1
0.0008*
0.16
mI/NAA
(0.11)
0.49
(0.06)
0.38
(0.06)
0.41
< 0.0001*
< 0.0001*
0.003*
0.29
mI/Cho
(0.11)
1.09
(0.05)
0.97
(0.04)
1.04
0.003*
0.19
0.0008*
0.09
śr. FA
(0.15)
0.559
(0.11)
0.612
(0.07)
0.673
< 0.0001*
< 0.0001*
0.0002*
0.0003*
rCBV
(0.05)
1.09
(0.04)
1.21
(0.04)
1.28
< 0.0001*
< 0.0001*
0.0003*
0.04*
(0.13)
(0.09)
(0.1)
MRS
PWI
LSD Tukey’s test, p values
AD vs
AD vs
MCI vs
CG
MCI
CG
< 0.0001* < 0.0001*
0.74
ANOVA
p value
NAA/Cr
DTI
Mean values (SD)
DTI + PWI
Posterior
cingulum
Mean values (SD)
LSD Tukey’s test,
ANOVA
p value
AD
MCI
CG
śr. FA
0.559
0.612
0.673
< 0.0001*
p values
AD vs CG AD vs
MCI
< 0.0001* 0.0002*
rCBV
(0.05)
1.09
(0.04)
1.21
(0.04)
1.28
< 0.0001*
< 0.0001*
(0.13)
(0.09)
(0.1)
mean FA
0.0003*
MCI vs
CG
0.0003*
0.04*
rCBV
0,8
1,6
0,7
1,4
0,6
1,2
0,5
1
0,4
0,8
0,3
0,6
0,2
0,4
0,1
0,2
0
0
AD
MCI
CG
AD
MCI
CG
PWI vs DTI vs PET –
preliminary results
• comparison of the accuracy of FDG PET, PWI and
DTI in cingulate gyrus in AD and MCI patients and
controls
PWI vs DTI vs PET – preliminary results
z score:
mean value in control group - mean value in patients’ group
___________________________________
mean standard deviation in the healthy controls’ group
PET
PWI
DTI
AD
1,69
1,90
2,60
MCI
0,76
0,70
1,48
DTI > PET
DTI > PWI
PWI = PET
p<0,05
p<0,05
CONCLUSIONS
•
Multisequential MR protocol, including plain
MRI, MRS, PWI and DTI provides better
assessment of the brain structures’ impairment in
dementia and enables differentiation of AD
from MCI and MCI from healthy individuals
CONCLUSIONS
• MRS, PWI and DTI measurements in
posterior cingulum can reliably differentiate
AD and MCI, with the highest accuracy of
DTI, followed by PWI and MRS
• Perfusion CT is an efficient method in
differentiating AD from VaD and evaluating of
the severity of dementia and thus may be used
additionally in diagnostic process
THANKS FOR YOUR
ATTENTION
Acknowledgments:
- Jerzy Leszek
- Anna Czarnecka
- Elżbieta Trypka
- Adam Macioszek