Faculty Collaboration Database

Radial diffusivity predicts demyelination in ex vivo multiple sclerosis spinal cords. Neuroimage 2011 Apr 15;55(4):1454-60

Date

01/18/2011

Pubmed ID

21238597

Pubmed Central ID

PMC3062747

DOI

10.1016/j.neuroimage.2011.01.007

Scopus ID

2-s2.0-79952735821 (requires institutional sign-in at Scopus site)   302 Citations

Abstract

OBJECTIVE: Correlation of diffusion tensor imaging (DTI) with histochemical staining for demyelination and axonal damage in multiple sclerosis (MS) ex vivo human cervical spinal cords.

BACKGROUND: In MS, demyelination, axonal degeneration, and inflammation contribute to disease pathogenesis to variable degrees. Based upon in vivo animal studies with acute injury and histopathologic correlation, we hypothesized that DTI can differentiate between axonal and myelin pathologies within humans.

METHODS: DTI was performed at 4.7 T on 9 MS and 5 normal control fixed cervical spinal cord blocks following autopsy. Sections were then stained for Luxol fast blue (LFB), Bielschowsky silver, and hematoxylin and eosin (H&E). Regions of interest (ROIs) were graded semi-quantitatively as normal myelination, mild (<50%) demyelination, or moderate-severe (>50%) demyelination. Corresponding axonal counts were manually determined on Bielschowsky silver. ROIs were mapped to co-registered DTI parameter slices. DTI parameters evaluated included standard quantitative assessments of apparent diffusion coefficient (ADC), relative anisotropy (RA), axial diffusivity and radial diffusivity. Statistical correlations were made between histochemical gradings and DTI parameters using linear mixed models.

RESULTS: Within ROIs in MS subjects, increased radial diffusivity distinguished worsening severities of demyelination. Relative anisotropy was decreased in the setting of moderate-severe demyelination compared to normal areas and areas of mild demyelination. Radial diffusivity, ADC, and RA became increasingly altered within quartiles of worsening axonal counts. Axial diffusivity did not correlate with axonal density (p=0.091).

CONCLUSIONS: Increased radial diffusivity can serve as a surrogate for demyelination. However, radial diffusivity was also altered with axon injury, suggesting that this measure is not pathologically specific within chronic human MS tissue. We propose that radial diffusivity can serve as a marker of overall tissue integrity within chronic MS lesions. This study provides pathologic foundation for on-going in vivo DTI studies in MS.

Author List

Klawiter EC, Schmidt RE, Trinkaus K, Liang HF, Budde MD, Naismith RT, Song SK, Cross AH, Benzinger TL

Author

Matthew Budde PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Female
Humans
Image Interpretation, Computer-Assisted
Magnetic Resonance Imaging
Male
Middle Aged
Multiple Sclerosis
Nerve Fibers, Myelinated
Reproducibility of Results
Retrograde Degeneration
Sensitivity and Specificity
Spinal Cord