1/7/2013

1

MR and CT Imaging, Part II

Differential diagnostic evaluation of white matter disorders

Joshua P. Klein, M.D., Ph.D.Departments of Neurology and Radiology

Brigham and Women’s Hospital and Harvard Medical School

American Society of Neuroimaging36th Annual Meeting, Las Vegas, NV

American Society of Neuroimaging36th Annual Meeting, Las Vegas, NV

Disclosures

No financial disclosures relevant to this presentation

Author and Editor compensation and royalties from McGraw-Hill and Oakstone Publishers

Approach to imaging

I. Pattern recognition

II. Acute vs. chronic abnormalities

III. Longitudinal changes

WHITE MATTER

Optic nerves and pathways

Corpus callosum

Cerebral/cerebellar peduncles

Medial longitudinal fasciculus

Posterior columns

Pyramidal tracts

GRAY MATTER

Basal ganglia and thalamus

Juxtacortical & cortical

statdx.com

I. Pattern recognition

1/7/2013

2

I. Pattern recognition

Klein JP, ACP Medicine 2012

I. Pattern recognition

Klein JP, ACP Medicine 2012

Intra-cortical and deep gray matter lesions

1) Difficult to detect due to reduced contrast between normal and affected GM (compared to WM)

2) Majority of lesions occur adjacent to cortical veins

3) Intra-cortical demyelination occurs as much as WMdemyelination in SP MS, and more than WMdemyelination in PP MS.

4) GM lesions likely contribute independently to clinicaldisability

Neurologist 2011;17:185J Neurol Sci 2005;233:55

I. Pattern recognition I. Pattern recognition

History / lab red flagsa. onset age < 10 or > 50b. clinicoradiographic mismatchc. hearing lossd. progressive or acute onsete. seizures at onsetf. simultaneous bilateral vision loss g. complete transverse myelitish. elevated ESRi. CSF protein > 100 and/or CSF WBC > 50j. h/o rheum, autoimmune, or psych diagnoses

1/7/2013

3

Neurology 2012;79:S1

I. Pattern recognition I. Pattern recognition

History / lab red flags

I. Pattern recognition

Imaging red flagsa. hypercellularityb. hemorrhagec. infarctiond. necrosise. unusual lesion appearancef. unusual enhancement patterng. hypervascularityh. infiltration/membrane turnover

Neuromyelitis optica

Longitudinally extensive central cord lesionsBilateral or sequential optic neuritis is more common

than in MS

1/7/2013

4

Sarcoidosis

CSF normal, no OCBs, serum ACE elevated5-15% involvement of CNS

Behçet disease

CSF lymphocytic pleocytosis, no OCBs Relapsing course, brainstem lesions are common

Cobalamin deficiency

Seen in pernicious anemia (anti-parietal cell Abs), and after gastric bypass. Copper deficiency and nitrous oxide exposure can produce similar lesions.

Lupus

+ANA, +dsDNA, elevated APLA IgM, and 3 OCBs

1/7/2013

5

Primary CNS vasculitis

Lymphocytic pleocytosis, ESR nl, biopsy negative; relapsing course; can see enhancing lesions

CADASIL

Notch-3 gene mutation. +FH of early strokes

Anaplastic astrocytoma (multicentric)

Hypercellularity, hypervascularity, and necrosis are atypical for MS

Intravascular lymphoma

Small vessel vasculitis, CSF lymphocytic pleocytosis, angiogram negative. Skin and kidneys involvement.

1/7/2013

6

Migraine

Clinical, epidemiologic, radiographic overlap with MS

Meier DS, et al. AJNR 2007;28(10):1956-63 Meier DS, Guttmann CR. NeuroImage 2006;32(2):531-7

Demyelination is dynamic

T1 PD T2

T2

PD

T1

II. Acute vs. chronic abnormalities

II. Acute vs. chronic abnormalities

Re-identify all previously seen lesions (T1 & T2)

Identify any new lesions (T1 & T2)

Identify acute demyelination (T1-post & DWI)

Identify non-lesional volumetric changes (T1 & T2)

Reporting: interval or acute demyelination

1.5T 3.0T

1/7/2013

7

T1-post T2-FLAIR

II. Acute vs. chronic abnormalities

Neurology 2000;54;1427

II. Acute vs. chronic abnormalities

T1-post

T1-post DWI

FLAIR ADC

Radiographics 2006;26:S173

II. Acute vs. chronic abnormalities

Meier DS and Guttmann CR

III. Longitudinal changes

1/7/2013

8

III. Longitudinal changes

Can longitudinal MRIs predict clinical phenotype and future disability? Therapeutic response?

Parenchymal volume loss (absolute, rate of change)- gray matter fraction- white matter fraction- cervical spinal cord

White and gray matter lesion burden- T2 hyperintense lesions- T1 hypointense lesions

Bakshi R et al, Lancet Neurol 2008;7:615

III. Longitudinal changesvolume gain volume loss

Klein JP et al, AJNR 2011;32:1138

Quantifying atrophy in MS

Klein JP et al, AJNR 2011;32:1138

Quantifying atrophy in MS

1/7/2013

9

Quantifying atrophy in MS

cervical upper thoracic lower thoracic

Klein JP et al, AJNR 2011;32:1138 Klein JP et al, AJNR 2011;32:1138

Quantifying atrophy in MS

Opposing pathological processes impact CNS volume in MS

• volume loss due to neuronal/axonal degeneration/gliosis• volume gain due to inflammation/edema

Spot measurements of volume may be uninterpretable with respect to progression, disease activity, or prognosis.

Longitudinally, there is clearly accelerated volume loss in patients with all forms of MS compared to controls.

III. Longitudinal changes

JNNP 2011;82:1125

year 0 year 1 subtracted

new

regressed

enlarged

III. Longitudinal changes

1/7/2013

10

Bakshi R et al, Arch Neurol 2008;65:1449

III. Longitudinal changes

MRI-based continuous scale as a marker of MS disease severity, the “MRDSS”

- T2 lesion volume (T2LV) - T1 lesion volume (T1LV) - Brain parenchymal fraction (BPF)- T1:T2 lesion volume (assessment of lesion severity)

Distinguishes RR from SP phenotypes

Bakshi R et al, Lancet Neurol 2008;7:615

III. Longitudinal changes

DTI tractography of the descending corticospinal tracks

Giussani et al, Neuroimage 2010;52:217

Three cases of pediatric infiltrating glioma

tumor

Giussani et al, Neuroimage 2010;52:217

1/7/2013

11

Two cases of pediatric demyelinating disease

Giussani et al, Neuroimage 2010;52:217

Brainstem tuberculoma

Lyons JL et al, submitted

Summary

I. Pattern recognition

II. Acute vs. chronic abnormalities

III. Longitudinal changes