Visualization of Fibers at Risk for Neuronal Tract Injury in Early MS by Streamtube Diffusion Tractography at 3 Tesla

Jack H Simon 1

David E Miller 1

Mark Brown 1

John R Corboy 1

Jeffrey L Bennett 1

Song Zhang 2

David H Laidlaw 2

1University of Colorado Health Sciences Center 2Brown University

Supported by the National MS Society (RG 3307-A-1), GE Medical Systems,and the National Science Foundation (CCR-0086065).

Background – Neuronal Tract Degeneration in Early MS •Axonal injury in inflammatory MS Lesions

•Trapp et al 1998; Ferguson et al 1997•Empty myelin cylinders 2° to and distant from focal lesion

•Bjartmar et al 2001•Major axonal loss (and atrophy) in corpus callosum

•Evangelou et al 2000•Neuronal Tract Degeneration Patterns in Early MS

Transcallosal BandsCorticospinal Tract Degeneration

Bjartmar et al 2001

Simon et al Neurology 2000 Simon et al Neurology 2001

Goals/Question

• Develop a process to identify and then interrogate neuronal fibers that are anatomically related to focal demyelinating lesions

• Can we detect and measure neuronal fiber injury/degeneration in vivo ?

Strategy

• Earliest MS – Identify focal lesions at the time of a CIS

• Identify fibers transiting the focal lesion and reaching a distant structure (corpus callosum)

• Interrogate fibers (in corpus callosum) by MRI distant from focal lesion – MTR, Diffusion tensor (<D>; FA)– Longitudinal MRI follow-up

3T Pulse Parameters • Diffusion Tensor Imaging

– Echo-planar – B-value 1000, 25 gradient directions

• Axial plane - 3 sets of overlapping slices • 5.1 mm thick with 1.7mm shifts• FOV 28 x 28 cm, matrix 160 x160, 2 excitations • TR/TE 6075/69.8-minimum

• Magnetization Transfer Imaging– 3D gradient-echo

• MT pulse – Fermipulse; applied middle 30% of the phase encode steps (SAR) – Pulse width of 8 ms– Peak B1 field of 9.24 μT, flip angle of 670°– 1200 Hz from the center frequency– TR/TE/flip angle 50/2.4(fr)/15° – FOV 22x22, matrix 256 x192, one excitation

• Sagittal plane • 3 mm partitions

YesAt 1 yNo10.69+Optic neuritis26

F

3

YesAt 1m,3mNo2.99+Partial

transverse

myelitis

33

F

2

Yes At 3mNo5.83+Optic neuritis

OCB positive

38

M

1

TreatedNew MR lesions on follow-up?

CDMSBrain

T2 lesion

Volume

(cc)

DISCIS

Presentation

Age

Gender

Patient

OCB = oligoclonal bands DIS= fulfill McDonald criteria for dissemination in spaceCDMS =clinically definite MS based on second attack by 1.5 year follow-upTreated= Treatment with immunomodulatory therapy

Table 1 . Patient Characteristics

Patient Characteristics

Generate streamtubes and streamsurfaces •Westin et al 2002; Zhang et al 2003•coherent white matter tracts – fastest diffusion, principal eigenvector

Terminate streamtube•low linear diffusion; data boundary; curvature•500,000 streamtubes

Cull #1 –length; anisotropy; redundancy•2,000 streamtubes

Cull # 2 - seed points within the 3D coordinates of T2-lesions

Cull # 3 - intersection with corpus callosum.

Calculate Diffusion tensor - non-linear approach

Register data sets- affine transformations optimized by mutual information algorithm

Outline of Streamtube Tractography Strategy

Visualize in optimal projection – quantitative analyses

Visualization -Streamtubes + Streamsurfaces Segmentation & Registration

AAMI (Analysis Application for Medical Imaging)•David E. Miller - University of Colorado HSC

Visualization Tools •Song Zhang and David Laidlaw - Brown University

Streamtubes culled to lesionStreamsurfaces not utilized

Streamtubes culled to [lesion + corpus callosum]

Case 1

Streamtubes and Streamsurfaces Culled to Lesion Culled to [lesion + corpus callosum]

Culled to Lesion Culled to [Lesion + Corpus Callosum]

Case 2

Case 2

Culled to [lesion + corpus callosum]

Case 3

Case 1 Registration of culled streamtubes to sagittal representation of corpus callosum

Fibers at Risk (FAR)

  Corpus Callosum Area Mean MTR

ID FAR

%AAWM

%

AllCorpus

CallosumNAWMFraction

AAWMFraction

FARFraction

CIS 1 21.0 4.1 48.94 49.06 45.98 50.57

CIS 2 10.0 0 49.55 49.55   49.78

CIS 3 30.0 8.7 48.53 48.55 48.36 50.63

CIS 1 CIS 2 CIS 3

Conclusions

• Viable strategy and methodology to identify a new class of tissue called fibers at risk (FAR)– NAWM– AAWM– FAR

• FAR makes up a formidable percentage of corpus callosum with minimal overlap with AAWM

• Strategy applicable to any neuronal tract• Future studies to determine injury profile over time,

factors associated with more severe neuronal tract injury• Assay of MS neurodegeneration to evaluate treatment ?

Supported by

The National Multiple Sclerosis Society (RG 3307-A-1)GE Medical Systems (3T diffusion tensor MRI)National Science Foundation (CCR-0086065)

University of Colorado 3T Research Instrument (ONDCP)

University of Colorado Brain Imaging Research Laboratory (BIRL) Rebecca Leek and MaryJoel Meyer

BIRL and Brain Imaging Center for Drug Abuse Research Deb Singel