Thibo Billiet
E-poster nr. 3654
Tuesday 23 april at 13:30, Computer 54
Microstructural characterization of
Unidentified Bright Objects in
Neurofibromatosis type 1
Thibo Billiet1, Louise Emsell1, Burkhard Maedler2, Felice D'Arco3, Sabine Deprez1,
Judith Verhoeven1, Ellen Plasschaert4, Ronald Peeters1, Alexander Leemans5, Bea Van
den Bergh6, Mathieu Vandenbulcke7, Eric Legius4, and Stefan Sunaert1
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Translational MRI, Imaging and Pathology dpt., KU Leuven, Leuven, Belgium
Radiology, University Hospitals Leuven, Leuven, Belgium
Leuven research Institute for Neuroscience & Disease, Leuven, Belgium
Medical Imaging Research Center, KU Leuven & UZ Leuven, Leuven, Belgium
Division of Stereotaxy and MR-Based Operative Techniques, Department of Neurosurgery, Bonn University Hospital, Bonn, Germany
Radiology, University Federico II of Naples, Naples, Italy
Human Genetics, KU Leuven, Leuven, Belgium
Image Sciences Institute, University Medical Center Utrecht,Utrecht, The Netherlands
Psychology, KU Leuven, Leuven, Belgium
Psychiatry, KU Leuven, Leuven, Belgium
What are UBO’s?
Discussion
Research question
Conclusion
MWI results
Materials &
methods
DTI & DKI results
What are UBO’s?
Discussion
Research question
Conclusion
MWI results
Materials &
methods
DTI & DKI results
Unidentified Bright Objects are NF1-related T2 hyperintensities
Neurofibromatosis type 1:
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Hereditary genetic disorder
Prevalence 1 in 3000
Peripheral nerve tumours
Learning difficulties in children
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(transient) hyperintensities on
T2-weighted MRI scans
Cerebellar white matter
Basal ganglia and
hypothalami
Mesencephalon
Unidentified Bright Objects can be transient
UBO number vs. age
Cerebellar WM
Globus Pallidus /
Internal Capsule
Kraut M.A., Gerring J.P. et al., A.J.M.G. 129A:113-119 (2004)
UBO volume vs. age
Cerebellar WM
Globus Pallidus /
Internal Capsule
The histopathological basis of UBOs remains unclear
1H MR Spectroscopy
NAA:
UBO < contralateral NAWM
Choline: UBO > contralateral NAWM
Hamartomas?
Braffman, Bilaniuk et al. 1988
Jones, Gunawardena et al. 2001
Heterotopias?
Apparent Diffusion Coefficient (ADC)
UBO > contralateral NAWM
Tognini, Ferrozzi et al. 2005
Alkan, Sigirci et al. 2005
UBO > healthy control WM
Eastwood, Fiorella et al. 2001
Van Engelen, Krab et al. 2008
Fractional Anisotropy (FA)
UBO < healthy control WM
Zamboni, Loenneker et al. 2007
Ferraz-Filho, da Rocha et al. 2011
Filippi, Bos et al. 2012
Magnetization Transfer Ratio (MTR)
UBO < healthy control WM
Margariti et al. 2007
Bognanno, Edwards et al. 1988
Regions of abnormal
myelination/demyelination?
Smirniotopoulos and Murphy 1992
Intramyelinic
vacuolization/astroglial cell
proliferation?
DiPaolo et al. 1995
The histopathological basis of UBOs remains unclear
1H MR Spectroscopy
NAA:
UBO < contralateral NAWM
Choline: UBO > contralateral NAWM
Hamartomas?
Braffman, Bilaniuk et al. 1988
Jones, Gunawardena et al. 2001
Heterotopias?
Apparent Diffusion Coefficient (ADC)
UBO > contralateral NAWM
Tognini, Ferrozzi et al. 2005
Alkan, Sigirci et al. 2005
UBO > healthy control WM
Eastwood, Fiorella et al. 2001
Van Engelen, Krab et al. 2008
Fractional Anisotropy (FA)
UBO < healthy control WM
Zamboni, Loenneker et al. 2007
Ferraz-Filho, da Rocha et al. 2011
Filippi, Bos et al. 2012
Magnetization Transfer Ratio (MTR)
UBO < healthy control WM
Margariti et al. 2007
Bognanno, Edwards et al. 1988
Regions of abnormal
myelination/demyelination?
Smirniotopoulos and Murphy 1992
Intramyelinic
vacuolization/astroglial cell
proliferation?
DiPaolo et al. 1995
What are UBO’s?
Discussion
Research question
Conclusion
MWI results
Materials &
methods
DTI & DKI results
Can novel MRI techniques refine our understanding of UBO
microstructure?
DTI and DKI
UBO
vs.
cNAWM
?
MWI
Pairwise
comparison
What are UBO’s?
Discussion
Research question
Conclusion
MWI results
Materials &
methods
DTI & DKI results
Kurtosis Tensor Imaging
Diffusion Tensor Imaging
Diffusion Tensor Imaging & Diffusion Kurtosis Imaging
Radial diffusion
Excess Kurtosis = 0
Mean diffusion
Axial diffusion
Fractional
Anisotropy
No boundaries:
Free diffusion
Excess
Kurtosis =
0.5
Excess
Kurtosis = 5
Axial kurtosis
Mean kurtosis
Radial kurtosis
Kurtosis
Anisotropy
Myelin Water Imaging
A: the fraction of water with T2 relaxation time 10-40 ms correlates with the
myelin content. This is the Myelin Water Fraction (MWF)
B: The water having medium T2 (40-200 ms) is the intra- and extracellular water
fraction (IEF). Note: The T2 time of CSF is even longer and not shown in this
graph.
C: the sum of all T2 fractions gives the total water content (TWC).
D: the geometric mean T2 of the MWF peak (M-gmT2)
E: the geometric mean T2 of total water content (T-gmT2)
F: the geometric mean T2 of the IEF peak (IE-gmT2)
G: the peak width of the IEF peak (IE-pw)
Data acquisition
DKI sequence
MWI sequence
T2w-FLAIR
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SE-EPI
3 b0-images
B-shells:
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700 s/mm2 x 25
directions
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1000 s/mm2 x 40
directions
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2800 s/mm2 x 75
directions
δ/ Δ= 20ms/48.3ms
TR/TE= 7800ms/90ms
uniform voxel size= 2.5 mm
FOV= 240 x 240 x 125 mm3
data matrix= 96 x 96 x 50
SENSE factor = 2 in the
anteroposterior direction
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3D GraSE
32 echoes (TE1 = 10 ms, ΔTE
= 10 ms)
TR = 800 ms
32 slices (thickness 1mm)
FOV= 240 x 240 x 64mm3
data matrix= 240 x 240 x 32
EPI read-out factor = 3
Madler and MacKay 2007
Prasloski, Rauscher et al. 2012
Poot, den Dekker et al. 2010
Subjects
• 7 NF1 patients (4 girls, 3 boys, mean age 12.6 years, SD 3.4 years)
• 21 UBO-cNAWM pairs (DKI) / 10 UBO-cNAWM pairs (MWI)
TR = 11000 ms
TI = 2800 ms
TE = 120 ms
Slice thickness 4 mm
FOV 230 x 184 x 119 mm3
Data matrix 240 x 138 x 16
What are UBO’s?
Discussion
Research question
Conclusion
MWI results
Materials &
methods
DTI & DKI results
DTI results
RD
MD
FA
RD
MD
FA
Increased diffusivity in radial direction is the main contributor to decreased
FA and increased MD in UBOs
AD --
No changes in axial direction
DKI results
RK
MK
KA
UBO
radial
compartmentalization
cNAWM
radial
compartmentalization
RK
MK
KA
Decreased kurtosis in radial direction is the main contributor to decreased
KA and decreased MK in UBOs
AK --
No changes in axial direction
What are UBO’s?
Discussion
Research question
Conclusion
MWI results
Materials &
methods
DTI & DKI results
MWI results
UBO
cNAWM
In UBOs:
1) Longer overall T2 relaxation time
MWI results
UBO
cNAWM
In UBOs:
1) Longer overall T2 relaxation time
2) Longer intra-and extracellular water T2
MWI results
UBO
cNAWM
In UBOs:
1) Longer overall T2 relaxation time
2) Longer intra-and extracellular water T2
3) Extended range of T2 times in intraand extracellular water
MWI results
UBO
cNAWM
In UBOs:
1) Longer overall T2 relaxation time
2) Longer intra-and extracellular water T2
3) Extended range of T2 times in intraand extracellular water
4) No changes in myelin water fraction
(MWF) or intra-and extracellular water
fraction (IEWF)
What are UBO’s?
Discussion
Research question
Conclusion
MWI results
Materials &
methods
DTI & DKI results
What can MWI teach us about the T2 hyperintensities (UBOs)?
UBO
cNAWM
T2 hyperintensities arise in the intra- and
extracellular space
• Longer T2 relaxation times
• Extended range of T2 times
 Edema?
Barnes et al. 1987 (T2 and cerebral edema), Margariti et al. 2007 (MTR in UBOs),
 Vacuolization?
Laule, Vavasour et al. 2007 (T2 and MS lesions)
 Astroglial cell proliferation?
DiPaolo et al. 1995 (diffuse proliferation of protoplasmic astroglia in UBOs)
Unaltered MWF
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No demyelination?
DiPaolo et al. 1995 (no effect on myelin stain in UBOs)
What is the added value of DTI & DKI?
UBO
cNAWM
MWI results: T2
hyperintensities arise in the
intra- and extracellular
space
Axial direction: no changes
 intact axons? DiPaolo et al. 1995 (no axonal damage in UBOs)
Radial direction: Increased diffusivity +
decreased kurtosis
 Intramyelinic vacuolization? DiPaolo et al. 1995 (spongiotic myelin
in UBOs)
What are UBO’s?
Discussion
Research question
Conclusion
MWI results
Materials &
methods
DTI & DKI results
Conclusion
DTI and DKI
UBO
vs.
cNAWM
cNAWM
MWI
UBO
Pairwise
comparison
DiPaolo’s hypothesis confirmed:
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No demyelination
No axonal damage
Intramyelinic vacuolization
Astroglial cell proliferation
Thank you for your attention
Translational MRI – Advanced Neuroradiology
Stefan Sunaert
Ronald Peeters
Louise Emsell
Sabine Deprez
Marjolein Verly
Silvia Kovacs
Sofie Van Cauter