MULTIPLE SCLEROSIS
NEW TECHNIQUES
Matilda A. Papathanasiou
Assist.professor of Neuroradiology
Dpt of Radiology
University of Athens Medical School
’’ΑΤΤΙΚΟΝ’’ University Hospital
.
OVERVIEW
• Review indications for imaging-protocol
• Review imaging findings in clinical setting
• New imaging techniques
– Findings
– Implications
– Limitations
MRI
WHO ?
HOW ?
MRI INDICATIONS Ι
1.
Initial evaluation after a CIS or based on
past history that is suspicious
2. Baseline imaging evaluation in MS
3. Spinal cord imaging
a. Symptoms s.c. (+ brain)
b. Findings in brain MR ?
J.H. Simon, D. Li, et al Standardized MR Imaging Protocol for Multiple Sclerosis:
Consortium of MS Centers Consensus Guidelines
AJNR Am. J. Neuroradiol., Feb 2006; 27: 455 - 461
MRI INDICATIONS ΙΙ
4. Follow up
1.
when clinical indications
a. Unexpected worsening
b. Reassess burden for initiation of Tx
c. Suspicion of secondary Dx
2. routine periodically (yearly) optional
5. Contrast
•
•
•
initial
baseline exam
Periodic follow up
J.H. Simon, D. Li, et al Standardized MR Imaging Protocol for Multiple Sclerosis:
Consortium of MS Centers Consensus Guidelines
AJNR Am. J. Neuroradiol., Feb 2006; 27: 455 - 461
Sequence
Diagnostic Scan
for CIS
Comment
1 3 plane (or other) scout
Recommended
Set up axial sections through
subcallosal line
2 Sagittal Fast FLAIR
Recommended
Sagittal FLAIR sensitive to early
MS pathology, such as in corpus callosum
3 Axial FSE PD/T2
Recommended
PD series sensitive to infratentorial lesions
that may be missed by FLAIR series
4 Axial Fast FLAIR
Recommended
Sensitive to white matter lesions and
especially juxtacortical–cortical lesions
5 Axial Gd enhanced T1
Recommended
Standard dose of 0.1 mmol/kg
scan starting minimum 5 min after injection
J.H. Simon, D. Li, et al Standardized MR Imaging Protocol for Multiple Sclerosis:
Consortium of MS Centers Consensus Guidelines
AJNR Am. J. Neuroradiol., Feb 2006; 27: 455 - 461
K. Kollia et al, AJNR, 30:699 –702 Apr 2009
‘’Black holes’’
MRI criteria dissemination in space
3 of 4
1. 1 Gd+ or 9 T2-hyperintense lesions if there is no
enhancing lesion
2. At least one infratentorial lesion
3. At least one juxtacortical lesion
4. At least 3 periventricular lesions
(Note: One spinal cord lesion can be substituted for one
brain lesion.)
McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple
sclerosis: guidelines from the International Panel on the diagnosis οf multiple sclerosis.
Ann Neurol 2001;50:121–27
PERIVENTRICULAR - JUXTACORTICAL
JUXTACORTICAL
INFRATENTORIAL
MRI criteria dissemination in time
• 1. MRI > 3mo after clinical event,
Gd+ site # original
• 2. MRI > 3 mo after clinical event,
Gdrepeat MRI in additional 3mo
new Τ2
or new Gd+
McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple
sclerosis: guidelines from the International Panel on the diagnosis οf multiple sclerosis.
Ann Neurol 2001;50:121–27
ENHANCEMENT
SPINAL CORD
•
•
•
•
•
•
•
50-90% MS
up to 25% only site involved
cervical
dorsolateral, < 2 vertebral bodies
< half transverse diameter
Multifocal
Cord atrophy
DIFFERENTIAL DIAGNOSIS










Ischemic lesions (small vessel disease)
Migraine
Vasculitis collagen v d
Encephalitis (ADEM, SSPE)
Trauma
Mets
Sarcoid
Dilated perivascular spaces VR
UBO (20%)
tumor (solitary lesions)
DIAGNOSIS
• MS is a clinical Dx
• MRI supports or provides alternative dx
?
Findings with increased specificity for
MS
Plaques along calososeptal interface and periventricular extension
(Dawson fingers) (sensitivity 93%, specificity 98%)
MA Gean et al. Radiology 1991 180:215-221
Lesions indicative MS
• Brain stem, subcortical, spinal cord
• Posterolateral pons, cerebelar
peduncles
• Enhancement MS vs small vessel
Combine MRI brain+spinal cord
BRAIN
CVD 17
CONNECTIVE TD 18
SLE 13
SJOGREN 7
SARCOID 5
INTERMED UVEITIS 6
MS(25)
O. Ν. D(66)
CORD
100%
92%
65%
6%
“In contrast to MS, cord lesions are very uncommon in OND. This
finding can help differentiate these disorders”
Bot J.C.,Barkhof F.et al Differentiation of Multiple Sclerosis from Other Inflammatory
Disorders and Cerebrovascular Disease: Value of Spinal MR Imaging Radiology 2002
223: 46-56;
CLINICORADIOLOGIC PARADOX
• Poor correlation of conventional
imaging/clinical
• MRI 4-10x more sensitive in
detecting lesions /clinical
• Gd enhancement 5-10x /clinical
NEW TECHNIQUES
Volumetric MRI
Magnetization transfer
Diffusion Tensor Imaging
MR Spectroscopy
Cortical imaging
Functional MRI
NEW TECHNIQUES
Volumetric MRI
Magnetization transfer
Diffusion Tensor Imaging
MR Spectroscopy
Cortical imaging
Functional MRI
VOLUMETRIC MRI
– LESION LOAD
•
•
total lesion volume Τ2, T1
total lesion activity enhanced Τ1
– BRAIN ATROPHY
VOLUMETRIC MRI
LESION LOAD (T2 lesion)
• T2 lesion volume increases 10%/year
in early RRMS
• T2 lesion load SPMS > RRMS
• Clinical trial studies
however
• Τ2 lesions heterogenous
• Τ2 load does not include NAWM
VOLUMETRIC MRI
LESION LOAD (Τ1 lesion)
• Τ1 Gd lesion load RRMS > SPMS
• Τ1 lesion load (Gd or black holes)
correlate clinical outcome (EDSS)
better than Τ2
• Clinical trial studies
LESION LOAD
CONCLUSIONS
• Lesion load does not account for
patient’s functional state
• Information monitoring natural history
• Information monitoring treatment
effects
ATROPHY
40 y.o. woman
VOLUMETRIC MRI
ATROPHY
– Global 0.6-1.0% yearly MS ( 0.1-0.3% nl)
– Not reversible
– Early prognosis
– all MS subtypes, even early and CIS
– Cortex / WM
– GM volume loss affects different regions
RRMS/nl
Brain voxels with significant GM loss in MS patients are shown
in yellow (P < .05, corrected).
A. Giorgio et al Brain Atrophy Assessment in Multiple Sclerosis: Importance and
Limitations Neuroimag Clin N Am 18 (2008) 675-686
ATROPHY
CONCLUSIONS
– Correlates with clinical disability > lesion load
– Correlates with cognitive impairment
– Evident before clinical disability
– Multicenter trials
– Is the distribution of atrophy clinically
significant?
– programs ’’in-house’’
NEW TECHNIQUES
Volumetric MRI
Magnetization transfer
Diffusion Tensor Imaging
MR Spectroscopy
Cortical imaging
Functional MRI
MAGNETIZATION TRANSFER
So
Ss
MTR = [ (So–Ss) / So] x 100%
proportional to concentration of myelin
PD with MT saturation
pulse
PD without MT
saturation pulse
ROI traced around lesions
Copied on images without MT
MTR lesions, ΝAWM
• MTR the first measurable abnormality not seen on
conventional MRI ΝΑWM
• T1 black hole <Τ1 isointense < perilesional < remote <
ΝΑWM < nl
• progressive
•
ΜΤR till a new lesion on Τ2
ΜΤR on follow-up 1-4 yrs
MAGNETIZATION TRANSFER
IMAGING
NAGM
NAWM
CONTROLS > RRMS > SPMS
Ge Y, Grossman RI et al Magnetization transfer ratio histogram analysis of NAGM
and NAWM in multiple sclerosis: J Comput Assist Tomogr 2002; 26: 62 - 68.
MTR
CONCLUSIONS
•
•
•
•
•
Measurable marker MS # nl
Diffuse pathology ΝΑWM, NAGM **
Monitoring disease - treatment
Histograms differ in clinical subtypes
Gray matter MTR reductions correlate with cognitive
tests
• NOT
• Individual patient management
• Clinical practice
• Need standardize (sequence, RF pulse, coils)
• Multicenter trials
NEW TECHNIQUES
Volumetric
Magnetization transfer
Diffusion Tensor Imaging
MR Spectroscopy
Cortical imaging
Functional MRI
Diffusion
ADC quantification
Diffusion
FRACTIONAL ANISOTROPY direction
FA map
Diffusion Tensor Imaging
• Information
– Tissue microstructure and architecture
including size, shape and organization
– Quantitative method for evaluating tissue
integrity
– FA info basis for fiber tractography
i.e. anatomic pathways of white matter
connectivity
FIBER TRACTOGRAPHY
MS
CONTROL
Reduced number of fibers when they traverse
white matter lesions in the patient
DTI lesions
• Lesions ADC and FA which indicates
disruption of myelin and axonal
structures that leads to disorganization
and increase in extracellular space
• Highest ADC in black holes
• SPMS > RRMS
DTI NAWM
• Lesion > NAWM perilesional > remote > nl
• Corpus callosum > NAWM wallerian
• Histogram for global DTI
Diffusion Imaging
CONCLUSIONS
• Measurable marker MS # nl
• Generalized pathology
• Need standardize
• Multicenter trials
NEW TECHNIQUES
Volumetric
Magnetization transfer
Diffusion Tensor Imaging
MR Spectroscopy
Cortical imaging
Functional MRI
SPECTROSCOPY
•
NAA in chronic plaques, ‘’black holes’’
• in acute plaque NAA
is partially reversible
– Cho, Lac, MI
• NAWM, progress to new lesion
• The regional changes in all the metabolites are dynamic
and variable over time and should be interpreted with
caution
SPECTROSCOPY WBNAA
• Quantification whole brain ΝΑΑ
• RRMS < controls
• Loss ΝΑΑ 3,6x faster than atrophy
precedes??
SPECTROSCOPY
CONCLUSIONS
• Measurable marker MS # nl
• Reversible
• Generalized pathology WBNAA
• Need standardize
• Multicenter trials
NEW TECHNIQUES
Volumetric
Magnetization transfer
DiffusionTensorImaging
MR Spectroscopy
Cortical imaging
Functional MRI
CORTICAL IMAGING
CORTEX
• DIR demonstrates cortical lesions
• >1.5T
• volumetry atrophy cortex
• MTR, DTI, NAA measurable markers in
cortex MS # nl
• f-MRI plasticity
•Lesions in the cortex
8Τ
1,5Τ
A. Kangarlu, E.C. Bourekas, A. Ray-Chaudhury, and K.W. Rammohan
Cerebral Cortical Lesions in Multiple Sclerosis Detected by MR Imaging
at 8 Tesla AJNR Am. J. Neuroradiol., Feb 2007; 28: 262 - 266.
NEW TECHNIQUES
Volumetric
Magnetization transfer
Diffusion Tensor Imaging
MR Spectroscopy
Cortical imaging
Functional MRI
controls
CIS
Maria A. Rocca,et al Evidence for axonal pathology and adaptive cortical reorganization
in patients at presentation with clinically isolated syndromes suggestive of multiple
sclerosis NeuroImage, 18, 2003, Pages 847-855
f-MRI
• visual, motor cognitive tasks
• Cortical reorganization does occur CIS, RR,
PPMS
• Extent of activation correlates with
degree of structural damage
• more activation
bilateral
complex tasks
Role of functional cortical
reorganization
• Adaptive role
compensation
recovery,
• Failure or exhaustion with increasing
disease duration or burden
irreversible disability
CONCLUSIONS Ι
CLINICAL APPLICATION
• MS is a clinical diagnosis
• MRI supports the diagnosis or provides
alternative dx
• Conventional sequences
– reproducible positioning, protocol
CONCLUSIONS ΙΙ
NEW TECHNIQUES
• Lesion load, ΝΑWM, MTR ,WBNAA
•
•
•
•
•
•
Volumetry
MT
DTI
Spectroscopy
Gray matter
f-MRI
8T
f-MRI
SPEC
MRI
DTI
MTR
8T
MRI
f-MRI
SPEC
DTI
MTR
THANK YOU FOR YOUR ATTENTION