mri and multiple sclerosis in clinical practice

1. MRI & Multiple Sclerosis
in clinical practice
Robert
Lavayssière
Hanoi, Nov 2015

2. Summary
Ü Clinical approach
Ü Acquisition protocols
Ü Basic signs
Ü Refinements
Ü Differential diagnosis
Ü Take home

3. Epidemiology
• Northern Europe & North America > other regions
• Europe: Prevalence: 83/10 000, Incidence: 4,3/100 000
• Sex Ratio: 2W/1M

4. Clinical aspects
Ü 2 main forms
Ü Relapsing Remitting RR: 58 %
Ü Symptoms > 24 h
Ü Interval > 1 month
Ü Complete or partial restoration
Ü Secondary Progressive SP: 27 %
Ü Progressive handicap
Ü Progression over 6 months
Ü Other forms
Ü Primary Progressive PP: 15 %
Ü Progressive Relapsing: PR
Handicap scale EDSS
RR & SP: earlier beginning 29 vs 40 y
M > W in PP form
Partnership between clinicians,
neurologist and/or ophtalmologist,
and radiologist

5. Imaging Protocols: brain
Ü T1 2D or 3D before injection (black
holes, baseline before IV)
Ü Axial Flair 2D or 3D
Ü Sagittal: Flair, T2, STIR
Ü Axial T2 thin slices on Posterior Fossa
Ü T1 3D SE post IV Delay between
Gd CA injection and acquisition: 10
minutes
Ü Optional: Magnetization
Transfer post-IV, Diffusion,
Spectroscopy, SWI
• Many systems, many sequences
• 1,5 vs 3T: 3D +++
• Know your system: tricks and traps

6. Imaging Protocols: medulla
Ü Inaugural
Ü T2 sagittal large FOV no FS
Ü STIR sagittal small FOV
Ü T1/T1 IV small FOV
Ü T2* axial
Ü T1 axial post IV
Ü Known MS
Ü STIR sagittal small FOV
Ü T1 sagittal small FOV
Ü T1 sagittal small FOV post
IV, if needed
Ü T2* axial

8. Safety / (Nephrogenic Systemic Fibrosis)
GFR > 60 mL/
mn
GFR 30-59 mL/
mn
GFR < 30 mL/
mn
High-risk:
Omniscan,
OptiMark,
Magnevist
OK Warning Contra-
indicated
Medium risk:
MultiHance,
Ablavar,
Primovist
OK OK
Should be
avoided
Low-risk:
Dotarem,
Gadovist,
ProHance
OK OK Warning

9. Evidence of Tissular Gd deposition
Gadolinium deposits in
the brains of patients
without renal disease:
- Xia et al. 2010
- McDonald et al. 2015
- Kanda et al. 2015
Gadolinium deposits in the
eyes of NSF patients
- Barker-Griffith et al. 2010
Gadolinium deposits in the
skin of NSF patients
- Thakral & Abraham 2009
- Birka et al. 2015
Gadolinium deposits in the
liver, lung, kidney, heart of
NSF patients :
- Sanyal et al. 2011
- Swaminathan et al. 2008
Gadolinium deposits in
the femoral bones of
patients after hip surgery:
- White et al. 2006
- Darrah et al. 2009
- Goto et al. 2015

10. GBCAs and Gd Deposition
Ü What we know
Ü Linear GBCAs induce T1 hypersignals in brain. Macrocyclic GBCAs do not
Ü This effect results from gadolinium deposition. It may last for months
Ü It is dose dependent but not strictly limited to multiple (≥ 6) injections
Ü It does not require a blood brain barrier disruption nor renal dysfunction
Ü Long-term retention has also been observed in patients‘s bones and skin
Ü Linear and macrocyclic GBCAs display different tissular kinetic profiles
Ü What we do not know
Ü Has gadolinium deposition any consequence on brain function or integrity?
Ü Are there some more at-risk patients?
Ü How long should we wait until symptoms occur? Should we wait and see?

11. New sequence
Ü DDIR
Ü DWI

12. 3D DIR
DIR = Double inversion
recupera4on
Ü TI: 450 to 625 ms : SB
Ü TI: 2600 ms : LCS
Ü Resolu4on 1 mm (3D, 3T)

13. Double inversion recuperation DIR
• Fat and water nulling
• Better visualization of
cortical/sub-cortical lesions
• Low S/N
• Some artifacts
DIR
FLAIR

14. T2* / Imagerie de susceptibilité
SWI et veinules
SWI et veinules

15. MS imaged

16. Plaques ?
Inflammation Demyelinization Gliosis Axonal loss
T2 High signal High signal High signal High signal
T1 Low signal Low signal
Gd + ? Gd -

17. MS or not?
Ü High signal intensity zone: NOT specific !
Ü Probably MS
Ü Ovoïd (not “nodular/round”)
Ü Corpus callosum lesion (sagittal +++)
Ü Perpendicular to ventricles
Ü Dawson’s digitation
Ü (Asymptomatic) medullar lesion (s)
Ü Not MS (importance of clinical information and biology)
Ü Contrast enhancement lasting > 3 months
Ü Mass effect
Ü Meningeal enhancement

18. High signal intensity zone in MS
Ü Shape
Ü Ovoid
Ü Perpendicular to ventricles
Ü Variable in size, mm to cms
Ü Halo = oedema
Ü Confluence
Ü Topography
Ü Periventricular: lateral, temporal
Ü Sub-cortical: U fibres
Ü Optic nerve (STIR,T2 HR)
Ü Infra-tentorial:
Ü middle cerebellar peduncle
Ü V4 floor
Ü Pons

21. 27 YO F
Non specific symptoms
Referred by GP for LL weakness
Pulmonary embolism post delivery
Birth control : pill

23. 30
YO
Female
Lower
Limb
Weakness
3D 1mm thickness

24. RR MS3D 1mm reconstructed
MT

25. Cortical and sub cortical: DIR>FLAIR
Nelson et al. Am J Neuroradiol 2007

27. Enhancement
Ü “Biomarker”: active inflammation
Ü Early sign, tends to decrease
Ü BBB lesion
Ü Short time span < 3 months,
between 3 w to 1 month
Ü Parallel to size of lesion (s)
Ü (No need to inject higher dose) Annular
C shape
Nodular

28. HR MR veinographie (SWI)
Venula
Plaque
Dawson J. Trans Roy Soc
Edinb 1916
Ormerod et al. Brain. 1987
Peri veinous: Dawson’s fingers

29. FLAIR/DWI

30. Low signal
Ü Acute: oedema. Regression ?
Ü Chronic: “black holes”
Ü Destruction/atrophy
Ü Large plaques
Ü Associated with enhancing and
non enhancing plaques
Ü May be associated, up to 50 %, with
Ü lipid deposits in macrophages :
high signal rings
Ü iron deposits: T2*/SWI signal loss

31. Traps and Tricks
Fosse postérieure : 2D VS 3D
2D FLAIR HR 3D FLAIR
T2 HR
FLAIR 2D vs 3D : 2D better detection,
but more flow artifacts = 3D : PF +++
Posterior fossa,
optic nerve:
thin slices, T2 HR

32. Traps and Tricks
3D T1 SE Better sensitivityFewer or no flow artifact
From Hodel & al

33. 2D Vs 3D FLAIR
3D T1 EG 3D DIR 1/5 3D FLAIR 1/5 2D FLAIR 4

34. Spectroscopy
Acute
Ü Inflammation, demyelinization,
neuronal disturbance
Ü Choline, lactate, lipids, myo-inositol
increase
Ü NAA, creatin decrease
Ü May precede plaque apparition on
MRi
Chronic
Ü Gliosis, neuronal loss
Ü (Sub)Normal spectrum, myo-inositol increase
Ü Neuronal loss: NAA decrease in “black
holes”

35. Medulla
Ü 80 % of RR have medullar
lesion (s) at early phase !
Ü Medullar lesion in 75 to 92 %
of MSs vs 6% in non MS WM
disease.
Ü Look for brain lesion and
vice versa
Ü Cervical: 50 %
Ü Postero-lateral, including gray
matter: not centered !
Ü Size: limited +++
Ü 2 vertebral height (sag) <
Ü Half medulla(axial) <
Ü Often multiple.
Ü High SI on T2, Iso on T1. Gd+ ?
Ü Medulla: normal, swollen,
atrophy…

36. 27 YO F Left LL anesthesia

37. Sequelae

38. Not so usual

39. Optic neuritis
STIR

40. Pseudo tumour
Chol/NAA<2
Long TE
JFR 2010
Chol
NAA
Lactate

41. 2 weeks later
BALO
J. Balo
1928

42. Clinical and Imaging Integration
Ü Barkhof
Ü ≥ 9 T2 HI lesions or 1Gd +
Ü 1 sub-cortical
Ü ≥ 3 peri-ventricular lesions
Ü 1 infra-tentorial lesion
80 % patients evolve toward MS
Ü Mac Donald (revised)
Ü Spatial spread: ≥ 1 T2 HI lesion in at least 2
out of 4 localization (periventricular,
juxtacortical, infra-tentorial, medulla)
Ü Temporal spreading:
Ü New T2 HI lesion and/or Gd+ at follow
up
Ü Simultaneous Gd - and Gd + lesions at
the same time
Ü Low reproductibility (Korteweg 2007)
Spreading ?
Temporal Spatial
Clinical
(RR/SP)
and/or MRI
Clinical
(new symptoms)
and/or MRI
MRI and MS
Ü MS suspected
Ü Confirm: CDMS
Ü Other diagnosis…
Ü MS not suspected: MS diagnosis
suggested
Ü Follow-up, research

43. Clinical value ? Follow up
Ü No correlation between
handicap and number of lesions
& evolution of EDSS
Ü No MRI difference between RR
and SP
Ü Initial prognosis ?
Ü Worse if multifocal
Ü Optic Neuritis : better
Ü Transverse myelitis do not evolve
toward MS in most cases
Ü Predictive value G+:
Ü Relapse rate: nb G+ initially
Ü No correlation between nb G
+ and EDSS score 12/24
months
Ü Poor prognosis/early Tt
Ü Inflammatory/heavy lesion
weight
Ü Sequela after first strike
Ü Severity of the strike
Ü UnderTt ß Interferon:
probability of failure % nb of
new lesions within one year

44. 2nd line treatment
Ü Pre Tt requirements : ≥ 1 Gd +
lesion or ≥ 9 T2 lesions
Ü Follow-up Tisabri (Natalizumab)
Ü Annual JCV* serology -, 3 to 6
months JCV +
Ü MRI evolution ?
Ü Tysabri : sub-clinical LEMP ???
(mortality = about 25 to 30 %)
Ü Gilenya (fingolimod): viral
encephalitis (some case report)
(* Polyomavirus)

45. Other diagnosis: not MS ???
Importance of clinical input
Ü Age/sex
Ü Type of onset
Ü Associated signs
Ü Infectious
Ü Biology
Multiple diagnosis
Unusual MRI signs for MS ???
Inflammatory/infectious +++
Ü HIV
Ü Neuro-Behcet
Ü Neuro-Sarcoïdis
Ü Lyme disease
Ü Gougerot-Sjögren
Ü Syphilis

46. Conclusion
Ü All that shines is not MS J
Ü Integration of clinical (and biological)
background with “compatible images”.
Ü Handle with care: beware of words…
Ü Follow-up: treatment ???