Fractional anisotropy (FA) images from a 31-year-old healthy man, showing upper (axial), middle (coronal), and lower (sagittal) orientations. Regions of higher intensity represent white-matter tracts. Examples of white-matter tracts are labeled. Areas where multiple white-matter tracts cross in different orientations, such as adjacent to the genu of the corpus callosum on axial view, appear lower in intensity because no single orientation predominates.

In order to link FA values to specific white-matter structures and regions, the FA image should be aligned with an independently collected high-resolution structural MR image that provides the template for defining the white-matter regions of interest. This is the best approach to confirm that the FA values are in fact located in white-matter regions and requires special techniques to ensure accurate and valid matching of FA and structural images.

Another measure that can be computed with DTI is intervoxel rather than intravoxel coherence. This is the degree to which diffusion in neighboring voxels has a common orientation. This measure is similar to FA but views coherence on a larger spatial, voxel-to-voxel scale.

Application to Alcoholism

Although DTI has revealed white-matter abnormalities in certain neuropsychiatric conditions such as Alzheimer's disease, schizophrenia, AIDS, and depression, as well as in normal aging, DTI has only recently been used to examine brain white-matter microstructural integrity in alcoholism. Selective white-matter degradation associated with alcoholism is well established from neuropathological reports. DTI offers an especially relevant and safe imaging method to track the condition of white-matter microstructure over the course of alcoholism.

Research using DTI shows that, relative to age-matched control subjects, alcoholic men have lower regional FA, meaning that diffusion is less oriented in a single direction, in the front part (genu) of the corpus callosum and in the mass of white matter that composes the interior of the cerebral hemisphere (the side of the cerebrum; i.e., the centrum semiovale).

These DTI-detected white-matter abnormalities were functionally relevant; working memory correlated positively with FA in the white-matter region in the back part of the corpus callosum (the splenium), whereas attention scores correlated positively with intravoxel coherence in the genu. A study of alcoholic women revealed regional abnormalities in white-matter microstructure not detectable with MRI macrostructural measures of size. These results provide in vivo evidence that alcoholism disrupts white-matter microstructure and suggest that the interruption of both intra- and intervoxel coherence contributes to deficits in attention and working memory associated with chronic alcoholism. It remains to be determined whether DTI measures of white-matter integrity parallel the increase in white-matter volume that has been associated with maintaining abstinence or the further decrease of white-matter volume associated with relapse after detoxification.

Conclusion

Conventional MRI and DTI modalities each quantify different aspects of brain macrostructure and microstructure. When used together to assess patients when they first stop chronic heavy drinking, and again after longer periods of sobriety or possible relapse, MRI and DTI represent a powerful means of characterizing brain changes at different stages of alcoholism. The different types of information provided can be used to test hypotheses about the factors underlying improvement with prolonged abstinence from alcohol or deterioration with resumption of drinking. For example, low levels of FA in white matter may signify reversible demyelination and axonal deterioration or permanent axonal degeneration. If retesting shows an increase in FA (increased orientation in one direction), this may suggest remyelination or regrowth of neuronal processes.

Behavioral studies could include tests that assess functions of cortical regions connected by the white-matter pathways found to be disrupted by alcoholism and then improved with abstinence. Patterns of recovery and deterioration derived from such in vivo neuroimaging studies may provide clues to cellular mechanisms underlying reversible and permanent brain structural and functional changes occurring during the course of alcoholism.

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Tags: Alcoholism

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