Imaging of White Matter Diseases - WFNRS - 09.00/33-Miki...MS in Asia •1/3 of patients have...

Imaging of White Matter Diseases

ⅩⅨSymposiumNeuroradiologicum

Yukio MikiOsaka City University

Outline

1. MRI in MS (Introduction)

2. Conventional MRI in MS

3. MRI in MS diagnostic criteria

4. MRI of MS in Asia

5. MRI variations in MS

6. Non-conventional MRI in MS

7. MRI as a biomarker in MS

8. MRI in NMO

9. Diagnosis of ADEM

MRI in MS

• MRI lacks specificity but has high sensitivity; established as a most important “paraclinical test”

• Important in the new diagnostic criteria

• Many new MR technologies have been first applied for MS

– Ex. FLAIR, MTR, double IR

• Biomarker

Outline








8. MRI in NMO


T2WI, FLAIR

• Hyperintense: edema, inflammation, demyelination, axonal loss can be hyperintense; lacks specificity

• Slightly hyperintense: dirty-appearing WMGe, et al. AJNR 2003;24:1935-40Vrenken, et al. AJNR 2010;31:541-8

• Isoinitense: normal-appearing WM: microscopical demyelination and/or axonal loss

• Hypointense: iron deposition? (putamen, thalmus)

T1WI• Hyperintense

(free radical? Foam cell? Ferritin?)

– Periphery of active lesions

– Dentate nucleus

• 20% of MS patients (esp., SPMS)(Roccataglitata, et al. Radiology 2009;251:503-10)

• After brain irradiation(Kasahara, Miki, et al. Radiology, in press)

• Isointense: 80-90% of T2 lesions

• Hypointense: “T1-black hole” （10-20% of T2 lesions）：Axonal loss of severe demyelination

Roccataglitata, et al. Radiology 2009;251:503-10

Gd-enhanced MRI

• BBB breakdown;active lesions

• 5-10 times > clinical relapse

Outline








8. MRI in NMO


McDonald criteria

• Symptoms suggestive of MS

• Dissemination in space–Clinical information

–MR abnormality

• Dissemination in time–Clinical information

–MR abnormality

• No better explanation than MS

McDonald, et al. Ann Neurol 2001; 50:121-7Revised in 2005: Polman et al. Ann Neurol 2005; 58:840-6

MRI in McDonald criteria（2005 revised edition）

• MRI Criteria for Brain Abnormality (Dissemination in Space) – Three of four of the following:

1. One Gd-enhancing lesion or nine T2-hyperintense lesions if there is no Gd enhancing lesion

2. At least one infratentorial lesion3. At least one juxtacortical lesion4. At least three periventricular lesions• A spinal cord lesion can be considered equivalent to a

brain infratentorial lesion; an enhancing cord lesion to an enhancing brain lesion.

• MRI Criteria for Dissemination of Lesions in Time– Detection of an enhancing lesion at least 3 months

after the onset of the initial clinical event, not at the site corresponding to the initial event

– Detection of a new T2 lesion if it appears at any time compared with a reｆerence scan done at least 30 days after the onset of the initial clinical event

Swanton criteria

• Intended to increase the sensitivity for clinically isolated syndrome (CIS)

• Dissemination in space

– ≥ 2 of the followings

• Subcortical WM, periventricular WM, posterior fossa, spinal cord

• Dissemination in time

– New T2 lesion on follow-up MRI

• Higher sensitivity, almost equal specificity

• Hesitation among most clinicicians to adopt

Swanton et al. JNNP 2006;77:830-3Swanton et al. Lancet Neurol 2007;6:677-86

(Loevblad et al. AJNR 2010;31:983)

Outline








8. MRI in NMO


MS in Asia

• 1/3 of patients have optic-spinal MS or Devic disease

– Most of these patients are probably neuromyelitis optica (NMO).

• Fewer brain lesions than Caucasians

• Much fewer cerebellar lesions(Nakashima, et al. JNNP 1999;67:153)

• Fewer chronic progressive (primary or secondary progressive) MS patients

• More lesions with atypical MR finding

• Lower rate of positive CSF oligoclonal bands

– Patients with negative oligoclonal bands have more frequent atypical lesions, such as tumefactive MS or diffuse white matter lesions(Nakashima, et al. Mult Scler 2002;8:459)

MS diagnostic criteria in Japanhttp://www.nanbyou.or.jp/pdf/068_s.pdf

• Clinical symptoms more important than MRI for RRMS

• Same with McDonald criteria for PPMS

• Additional definitions for CPMS, Devic disease, optic-spinal MS andBalo’s concentric sclerosis

Proposed modifications to the McDonald criteria for use in Asia

Chong et al. Mult Scler 2009;15:887-8

McDonald criteria Proposed modifications for Asians

Spinal MRI

Spinal cord lesion should be under two

vertebral bodies in height

No restriction to length of spinal cord lesion

No swelling of the spinal cord lesion No restriction to spinal cord lesion with

swelling

Spinal cord lesion should occupy part of the

cross section

No restriction to spinal cord lesion involving

complete cross section

Brain MRI

Nine T2-hyperintense lesions or one

gadolinium-enhancing lesion

Four or more brain MRI T2-hyperintense

lesions in patients less than 60 years of age or

one gadolinium-enhancing lesion; or

more than one lesion in two or more typical

sites (juxtacortical, periventricular, posterior

fossa, and spinal cord)

Outline








8. MRI in NMO


MR variations in MS

• Ovoid lesion

• Enhancing lesion

• Callosal-septal interface lesion

• Isolated U-fiber lesion

• Tumefactive MS lesion

• Balo’s concentric sclerosis

• Spinal cord lesion

Ovoid lesions(Dawson's finger)

• Ovoid-shaped deep WM lesions parpendicular to the lateral ventricular wall

• Represent perivenous inflammation

• Frequent but not specific

Horowitz et al. AJNR 1989; 10:303-5

SWI @ 3T

T2WI @ 3T

Callosal-septal interface lesions (Subcallosal striations)

• Intracallosal lesions parpendicular to the ventricular wall

• High sensitivity and specificity

• Thin, sagittal FLAIR useful for MS diagnosis

Gean, et al. Radiology 1991; 180:215-21Palmer, et al. Radiology 1999; 210:149-53

FLAIR @ 3T

• MS lesions extending along the subcortical U-fibers

• About half of MS patients have at least one isolated U-fiber lesion

• Representing inflammation along the subcortical U-fibers?

• May be a cause of subcortical dementia

• Relatively specific for MS; adopted in McDonald’s criteria

Miki, et al. Neurology 1998; 50:1301Kidd, et al. Brain 1999; 122:17Rovaris, et al. AJNR 2000; 21:402

Pathology (PAS stain), Okazaki

Fundamentals of Neuropathology

T2WI

Gd

SWI @ 3T

Isolated U-fiber lesions

(Juxtacortical lesions)

Tumefactive MS

• Glioma (GBM)-like MS lesion (Lucchinetti, et al. Brain 2008;131:1759-75)

– Large size (>2 cm)

– mass effect

– ring ehhancement

• Biopsy is often required for final diagnosis, but possibility of MS should be considered to avoid aggressive surgery

One year after

FLAIR

T2WI Gd

Gd

Differentiation between tumefactive MS and GBM

• Less mass effect than GBM

• Open-ring sign(Masdeu,et al. Neurology 2000;54:1427; Metafratzi, et al. Neuroradiology 2002;44:97)

• Perfusion imaging(Cha, et al. AJNR 2001; 22:1109)

• Low density on noncontrast CT(Kim, et al. Radiology 2009; 251:467)

• No punctate hypointensity on SWI (Kim, et al, AJNR 2009;30:1574)

Gd SWI

• A rare variant of MS

• WM destroyed in concentric layers

• Formerly considered to be a monophasic rapidly progressive disease with a fatal outcome

• Increasing number of cases with better outcome (Karaarslan, et al. AJNR 2001;22:1362 )

• Relatively more frequent in China and Phillippines

• Very rare in Europe, US and Japan

Pathology (Myelin stain), Okazaki

Fundamentals of Neuropathology

Balo’s concentric sclerosis

DWI

T2WI @ 3T T1WI

Outline








8. MRI in NMO


Non-conventional MRI for MS

• Diffusion MRI

• High-field MRI, ultra high-field MRI

• Phase imaging

• SWI

• Double IR

• USPIO-enhanced MRI

28/86

Diffusion MRI

in MS

• Active MS lesions may be partially hyperintense on DWI(Tsuchiya, et al. EJR 1997;31:165Tievsky, et al. AJNR 1999; 20:1491Roychowdhury, et al. AJNR 2000;21:869)

– T2-shine through effect(Roychowdhury, et al. AJNR2000;21:869）

– Cytotoxic edema(Tievsky, et al. AJNR 1999; 20:1491）

• Decreased FA on DTI(Tievsky, et al. AJNR 1999; 20:1491)

Tievsky, et al. AJNR

1999; 20:1491

DWI ADC map

FA map

High-field (≥ 3T) MRI

• Higher SNR than 1.5 T

• More MS lesions detected– Sicotte, et al. Invest Radiol 2003;38:423-7

– Wattjes, et al. AJNR 2006;27:1794-8

30

MS @ 3T

31

MS @ 3T

32

MS @ 3T

Cortical MS lesions at 7T

Mainero, et al. Neurology 2009;73:941-8

Iron depositions and venous dilatations

shown on SWI in MS

Haacke, et al. JMRI 2009;29:537-44

Phase image at 7T

Hammond et al. Ann Neurol 2008;64:707-13

Cortical MS lesions on Double inversion recovery (IR)

• 2 times than SE T2WI, 1.5 times than FLAIR

Geurts et al. Radiology 2005;236:254-60

USPIO in MS(Dousset et al. AJNR

2006;27:1000-5)

• USPIO: ultrasmall particles of iron oxide

• Phagocytic activity

– High signal on T1WI, low on T2WI

USPIO-T2WI USPIO-T1WI

T2WI T1WI

Outline








8. MRI in NMO


• Relapses are relatively infrequent and poorlyrelated to disability accumulation

• Disability takes several years to accumulate

• Clinical scales are poorly reliable

MRI as a biomarker for MS

Why do we need surrogate tools to monitor MS evolution?

Why MRI as a surrogate?

• Sensitive (5-10 times > relapses)

• Objective

• Continuous values/Linear scale

• Close to “actual” pathology

• Reproducible

• Easy to blind and standardize

• Retrievable data

Courtesy of Dr. Massimo Philippi

Most widely used MR measurements for

clinical trials

• T2WI

– T2 lesion load

– New lesions

– Enlarging lesions

• Gd

– Total lesion number

– New lesions

– Enlarging lesions

Loevblad, et al. AJNR 2010;31:983-9

T2-volume measurement by Fuzzy Connectedness

Udupa, Wei, Miki, et al. IEEE T Med Imaging 1997;16:598-609

T2-lesion load in MS

• Not so correlated with clinical symptoms

– Miki, et al. Radiology 1999; 210:769-74

– Miki, et al. Radiology 1999; 213:395-9

– Kremenchutzky, et al. Brain 2006;129(pt 3):584-94

– Filippi, et al. J Neuroimaging 2007;17(Supple 1):3S-9S

– Fisniku, et al. Brain 2008;131:807-17

• Possible reasons

– T2 lesions correspond to various pathologies

– Normal-appearing, dirty-appearing WM

– Brain atrophy

Other MRI measurements used for

clinical trials

• T1 black hole

• Brain atrophy

• Spinal cord atrophy

• MTR (Whole brain MTR histogram)

• DTI

• MRS

• fMRI

Loevblad, et al. AJNR 2010;31:983-9

49/86

Whole brain MTR histogram in MS

• Peak height of whole brain MTRH represents the amount of normal WM (myelin)

• Different MTRH between MS patients and controls(van Buchem et al. AJNR 1997; 18:1287)

• MTRH peak height correlates with neuropsychological tests(van Buchem et al. Neurology 1998;50:1609)

• MTRH peak height correlates with EDSS in RRMS(Miki, et al. Radiology 1999; 210:769-74)

van Buchem et al. AJNR 1997; 18:1287 Miki, et al. Radiology 1999; 210:769-74

Outline








8. MRI in NMO


Neuromyelitis optica (NMO)

• Idiopathic, severe, demyelinating disease of the CNS that preferentially affects the optic nerve and spinal cord

• Formerly thought to be a variant of MS

• Specific antibody for NMO (NMO-IgG: aquaporin 4) -> distinct entity

• Pathologically, astrocytes are primally damaged (demyelination is secondary)

Diagnositic criteria for NMO

• Optic neuritis

• Acute myelitis

• ≥2 of the followings

–Longitudinally extensive myelitis (≥ 3 vertebral segments seen on MRI)

–Brain MRI not fulfilling MS criteria

–Positive AQP4

（Wingerchuk et al. Lancet Neurol 2007;6:805-15)

MS vs. NMO

Wingerchuk et al. Lancet Neurol 2007;6:805-15

MS NMO

Median age of

onset29 39

Sex (M:F) 1 : 2 1 : 9

MRI: brain Periventricular・Normal or non-specific

・Hypothalamic, brainstem

MRI: spinal

cord

・Short-segment

・Peripheral

・Longitudinally extensive

(≥ 3 vertebral segments)

・Central

NMO

T2WI Gd

T2WI

T2-hyperintense lesion density(MS vs. NMO)

• NMO: preferentially involves the central regions

• MS: preferentially involves the lateral and posterior regions

Nakamura, et al. J Neurol 2008; 255:163-70

NMO

MS

superimposed cord lesions

Brain

lesio

ns in

NM

O

Wingerchuk et al. Lancet Neurol 2007;6:805-15

Cloud-like enhancement in NMO

• Multiple patchy enhancing lesions with blurred margin

• 90% in NMO patients, 8% in MS patients

– Specific to NMO

• Possibly caused by primary involvement of the BBB by the autoantibodies

Ito, et al. Ann Neurol 2009;66:425-8

Outline








8. MRI in NMO


Acute demyelinating encephalomyelitis; ADEM

• Severe inflammatory demyelinating disease, frequently secondary to infection or vaccinations

• Usually monophasic

• May recur (multiphasic disseminated encephalomyelitis; MDEM)

• May evolve to MS

• How different from MS?

• Is there any “diagnostic criteria?

• Possible to differentiate from MS at the first attack?

Proposed criteria for differentiation between

ADEM and MS (>15 yrs old)(Multi-centered study in France)

• ≥2 of the followings -> ADEM

–Atypical clinical symptoms for MS• Consiousness alteration, hypersomnia, aphasia, seisure, hemiplegia, etc.)

–Absence of oligoclonal bands

–Gray matter involvement on MRI

• No significant difference in infectious episodes or vaccinations between ADEM and MS

De Seze et al. Arch Neurol 2007;64:1426-32

Role of MRI in the differentiation

of ADEM from MS in children

(<18 yrs old)

• ≥2 of the followings→MS

– Absence of a diffuse bilateral lesion pattern

– Presence of black holes

– Presence of two or more periventricular lesions

• Sensitivity:81%, Specificity:95%

• Follow-up at least 3 years (6 years for <11 years old) is recommended when diagnosed as ADEM

• Most useful for differentiating a first attack of MS from ADEM (Ketelslegers, et al. Neurology 2010;74:1412-1415)

Callen, et al. Neurology 2009;72:968-973

Summary

• MRI plays an important role in diagnosis of WM diseases (MS, NMO, ADEM).

• MRI is useful for biomarker in MS.

• There are differences in MRI of MS between Asian countries and western countries.

AcknowledgementsNew York University

- Robert I. Grossman

Kyoto University

- Mitsunori Kanagaki, Akira Yamamoto, Nobuyuki Mori, Seiko Kasahara, Takeshi Sawada, Emiko Morimoto, Kaori Togashi, Riki Matsumoto, Ryosuke Takahashi, Hidenao Fukuyama

Mie University

- Hidekazu Tomimoto

Tohoku University

- Kazuo Fujihara

Kyoto Min-iren Chuo Hospital, National Hospital Organization Utano Hospital, Irinoiin

- Takahiko Saida

University of Bordeaux

- Vincent Dousset

University Hospital San Raffaele

- Massimo Philippi

Osaka City University

- Taro Shimono, Tetsuo Nakayama, Kaeko Kitamura, Shinichi Sakamoto

Imaging of White Matter Diseases - WFNRS - 09.00/33-Miki...MS in Asia •1/3 of patients have...

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