MRI & Multiple Sclerosis

in clinical practice

Robert Lavayssière

Hanoi, Nov 2015

Summary

Ü  Clinical approach

Ü  Acquisition protocols

Ü  Basic signs

Ü  Refinements

Ü  Differential diagnosis

Ü  Take home

Epidemiology

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

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

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

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

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

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

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?

New sequence

Ü  DDIR

Ü  DWI

3DDIR

DIR=Doubleinversionrecupera4on

Ü  TI:450to625ms:SBÜ  TI:2600ms:LCSÜ  Resolu4on1mm(3D,3T)

Double inversion recuperation DIR

•  Fat and water nulling •  Better visualization of

cortical/sub-cortical lesions

•  Low S/N •  Some artifacts

DIR

FLAIR

T2* / Imagerie de susceptibilité

SWI et veinules

SWI et veinules

MS imaged

Plaques ?

Inflammation Demyelinization Gliosis Axonal loss

T2 High signal High signal High signal High signal T1 Low signal Low signal

Gd + ? Gd -

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

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

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

30 YO Female Lower Limb Weakness

3D 1mm thickness

RR MS 3D 1mm reconstructed

MT

Cortical and sub cortical: DIR>FLAIR

Nelson et al. Am J Neuroradiol 2007

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

HR MR veinographie (SWI)

Venula Plaque

Dawson J. Trans Roy Soc Edinb 1916 Ormerod et al. Brain. 1987

Peri veinous: Dawson’s fingers

FLAIR/DWI

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

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

Traps and Tricks

3D T1 SE Better sensitivity Fewer or no flow artifact

From Hodel & al

2D Vs 3D FLAIR

3D T1 EG 3D DIR 1/5 3D FLAIR 1/5 2D FLAIR 4

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”

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…

27 YO F Left LL anesthesia

Sequelae

Not so usual

Optic neuritis STIR

Pseudo tumour Chol/NAA<2

Long TE

JFR 2010

Chol

NAA

Lactate

2 weeks later

BALO

J. Balo 1928

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

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

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)

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

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 ???