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

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

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  1. Visualization of Fibers at Risk for Neuronal Tract Injury in Early MS by Streamtube Diffusion Tractography at 3 TeslaJack H Simon 1David E Miller 1Mark Brown 1John R Corboy 1Jeffrey L Bennett 1Song 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).

  2. 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 • Bjartmar et al 2001 Transcallosal Bands Corticospinal Tract Degeneration • Simon et al Neurology 2001 • Simon et al Neurology 2000

  3. Goals/Question • Develop a process to identify and then interrogate neuronal fibers that are anatomically related to focal demyelinating lesions • Can we detect and measureneuronal fiber injury/degeneration in vivo ?

  4. 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

  5. 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

  6. Patient Characteristics

  7. Outline of Streamtube Tractography Strategy Calculate Diffusion tensor - non-linear approach • 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. Register data sets- affine transformations optimized by mutual information algorithm Visualize in optimal projection – quantitative analyses

  8. Segmentation & Registration Visualization -Streamtubes + Streamsurfaces • AAMI (Analysis Application for Medical Imaging) • David E. Miller - University of Colorado HSC • Visualization Tools • Song Zhang and David Laidlaw - Brown University

  9. Streamtubes culled to lesion Streamsurfaces not utilized

  10. Streamtubes culled to [lesion + corpus callosum]

  11. Case 1 Streamtubes and Streamsurfaces Culled to Lesion Culled to [lesion + corpus callosum]

  12. Case 2 Culled to Lesion Culled to [Lesion + Corpus Callosum]

  13. Case 2

  14. Case 3 Culled to [lesion + corpus callosum]

  15. Fibers at Risk (FAR) Case 1 Registration of culled streamtubes to sagittal representation of corpus callosum

  16. CIS 1 CIS 2 CIS 3

  17. 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 ?

  18. 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

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