Radial diffusivity predicts demyelination in ex vivo multiple sclerosis spinal cords.
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.
Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA. eklawiter@partners.org
Eric C
EC
Klawiter
Robert E
RE
Schmidt
Kathryn
K
Trinkaus
Hsiao-Fang
HF
Liang
Matthew D
MD
Budde
Robert T
RT
Naismith
Sheng-Kwei
SK
Song
Anne H
AH
Cross
Tammie L
TL
Benzinger
D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000473:pathology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D015203:Reproducibility of Results; D012183:Retrograde Degeneration / Q000209:etiology* / Q000473:pathology*; D012680:Sensitivity and Specificity; D013116:Spinal Cord / Q000473:pathology*
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