Brain Damage in Alcoholics : MRI, Diffusion Tensor Imaging

by National Institute of Health

(Page 2 of 3)

Certain structural MR images of alcoholics show areas of greater brightness in white matter, called white-matter hyperintensities (WMHIs). These WMHIs can reflect a variety of underlying processes - including swelling caused by excess fluid (edema), the removal of the myelin sheath (demyelination), excess cell growth (gliosis), and increased extracellular fluid - some of which may eventually be documented and elucidated using DTI.

Long-term MRI studies of alcoholics in recovery or relapse have identified cortical white-matter volume as particularly amenable to recovery with abstinence or vulnerable to further decline with continued drinking. How volume is restored through abstinence or continues to decline with continued drinking remains unclear but probably involves changes in both myelination and axonal integrity.

Most early brain imaging studies of alcoholism were confined to male subjects. More recently, researchers have sought to determine whether women's brains are more or less vulnerable than men's to the damaging effects of alcohol abuse or dependence. A neuroimaging study that used computerized tomography (CT) showed comparable deficits in men and women, even though the women drank much less alcohol than the men. This finding, which suggested that women were more vulnerable to alcohol-induced brain damage, has been supported by some MRI studies measuring volumes of cortical white and gray matter and the fluid that bathes the brain and spinal cord (cerebrospinal fluid [CSF]). Other studies have not supported the idea of increased vulnerability among women. These later MRI studies highlight the importance of controlling adequately for gender-related differences in body/brain morphology and quantity and pattern of drinking. Furthermore, it is becoming increasingly apparent that brain tissue, especially white matter, that appears normal on MRI in alcoholic patients may in fact be affected by alcoholism.

Diffusion Tensor Imaging

DTI shows particular promise for assessing white-matter damage that is associated with excessive alcohol use, as indicated by both post mortem and in vivo studies.

Conventional MR images are "pictures" primarily of free water, the concentration of which differs by tissue type: White matter consists of about 70 percent water, gray matter 80 percent, and CSF 99 percent. These differences in water content contribute to the contrast between tissue types visible on structural images. DTI takes this imaging further by measuring differences in the freedom with which water molecules move within a tissue type and the amount and orientation of their diffusion, especially in white matter. With appropriate data collection and processing techniques, researchers can generate images that highlight white-matter tracts.

Water molecules are in constant motion. In regions such as the ventricles, relatively large fluid-filled spaces deep in the brain, which offer few or no physical constraints, movement occurs randomly in every direction. This random movement is described as isotropic (iso meaning "same" and tropic meaning "movement"). By contrast, water molecules in white-matter fibers are constrained by the physical boundaries of the axon sheath, which cause greater movement along the long axis of the fiber than across it. This movement is called anisotropic (aniso meaning "not the same").

How do we detect water diffusion in the brain with imaging? One way is to apply extra magnetic field gradients (diffusion gradients) during image acquisition to yield what is called a diffusion-weighted image. This process is analogous to looking through a microscope, focusing on some relatively motionless solid structures and some particles that are in Brownian motion, unfocusing briefly, and then refocusing the microscope on the same location. The solid structures will come back into focus, but some of the freely moving particles that have moved will be out of focus. In the ventricles, molecules are free to move out of focus. In the white-matter tracts, where axon sheaths restrict movement to one primary direction, it is less likely that molecules will move out of focus (there is less diffusion). Unlike the microscope, which has only one focus/unfocus direction, the scanner can focus and refocus in multiple dimensions by applying diffusion gradients in different directions. The researcher collects one image without gradients and then six images, each with diffusion gradients applied in a different direction.

The technique is called diffusion tensor imaging because a tensor, a mathematical description of the orientation and magnitude of diffusion, is computed for each voxel from the seven images. Further calculations result in three summary measures that reflect the magnitude or amount of diffusion in each direction. Trace images are based on the average diffusion in all three directions and illustrate the overall magnitude of diffusion; in trace images, the ventricles, which contain few obstructions to movement, are bright, and the gray matter and white matter are both dark.

Fractional anisotropy (FA) images are based on the extent to which one direction dominates; they illustrate the degree to which water molecules move in one predominant orientation. If diffusion is unconstrained (isotropic), FA is close to zero. If diffusion has one primary orientation (is anisotropic), FA can approach 1. Because diffusion follows their orientation, the long, thin, cable-like bundles of fibers making up white-matter tracts appear bright on the FA image.

FA images acquired in different planes will highlight different white-matter tracts or provide different views of them. Within a uniformly oriented tract, anything that disrupts the regular structure of white matter, such as loss of the protective myelin sheath or deterioration of the axons, might allow the water molecules to move more freely, resulting in decreased FA. Thus, lower-than-expected FA (which would indicate more isotropic diffusion) in a white-matter region of normal volume may reflect the loss of white-matter integrity resulting from a number of conditions, including aging and alcoholism.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.