Diffusion tensor imaging of neural tissue organization: correlations between radiologic and histologic parameters

Abstract

This study examined the relationship between histological variables and diffusion tensor imaging (DTI) values in a normal canine brain. We hypothesized that radial diffusivity (RD) would correlate with myelin density and fractional anisotropy (FA) would correlate with white matter fiber coherence. We acquired DTI maps of a normal canine brain post mortem on a 7T MR scanner (TR = 100 ms, TE = 18.1 ms, NEX = 1, width [d] = 4 ms, separation [D] = 8.9 ms, gradient amplitude = 600 mT/m, b=1,565 s/mm(2)) and generated maps of FA, RD, and axial diffusivity. The brain was subsequently sectioned and stained for myelin with gold chloride, which also allowed for measurement of fiber coherence. DTI metrics were then directly compared with the optical density of the myelin stain and the coherence of stained fibers. Multivariate linear regression demonstrated that RD, but not FA, significantly correlated with both myelin stain intensity (p = 0.031) and fiber coherence (p = 0.035). The Pearson correlation coefficient between these two histological variables and FA was 0.122; and was 0.607 for the histological variables and RD. We found that RD significantly correlated with both optical density of myelinated fibers and fiber coherence, but FA correlated with neither histological finding. Factors other than degree of myelination and fiber coherence should be considered to fully account for regional variation in FA.

Keywords: diffusion tensor imaging; myelination; tractography.

Figure 1

Light micrographs of 2 ROIs (40×) representing our finding that myelination status was much more strongly associated with RD values than with FA values. These histologic sections were stained with gold chloride, and a high intensity of the reddish-brown stain indicates areas with greater myelin content. We can visually appreciate that the left panel contained heavily myelinated tissue compared to the right, which contains only a few myelinated bundles. Among our ROIs, gold chloride optical densities ranged from 112 to 233. A) The corona radiata ROI, which had a high gold chloride optical density of 205, indicative of a high degree of myelination. Measured mean FA value in this ROI was moderate at 0.368 and mean RD value was quite low 1.80×10⁻⁴ mm/s. B) The caudate nucleus ROI, which had a gold chloride optical density value of 167, notably lower that measured at the site shown in A. Measured mean FA value in this ROI was 0.1222 (somewhat lower than the value seen at site shown in A) and mean RD value of 4.20×10 mm/s, much higher than shown in A).

Figure 2

Light micrographs of 2 ROIs (40×) of brain tissue stained with gold chloride showing various degrees of fiber coherence, representative of our finding that RD decreases with increasing fiber coherence but that FA did not necessarily increase with increasing fiber coherence. Among our ROIs, coherence measurements ranged from 0.0215 to 0.132. A) A region with low fiber coherence, containing stained fibers running in many directions, is shown. The ROI of the middle posterior limb of the internal capsule in which white matter fiber coherence was low, measuring 0.030. Mean FA was 0.571 and mean RD was 2.41×10⁻⁴ mm/s. B) A region with high fiber coherence, containing stained fibers predominantly oriented in a single direction, is shown. The ROI of the suprasylvian lobe white matter in which white matter fiber coherence was high, measuring 0.105. The corresponding ROI, which comprised the white matter bundle in the center of this micrograph, had a mean FA value of 0.353 and a mean RD of 1.82×10⁻⁴ mm/s.

Figure 3

Correlation of fractional aniosotropy with axial diffusivity (A) and radial diffusivity (B). Squares = gray matter ROIs, diamonds = white matter ROIs. There is a weak negative correlation between FA and axial diffusivity, but a very strong one with radial diffusivity.

Figure 4

Correlation of gold chloride optical density with fractional anisotropy (A) and radial diffusivity (B). Squares = gray matter ROIs, diamonds = white matter ROIs.

Figure 5

Correlation of fiber coherence with fractional anisotropy (A) and radial diffusivity (B). Squares = gray matter ROIs, diamonds = white matter ROIs.