Diffusion Tensor Imaging (DTI)

What DTI Shows About White Matter in the Brain

Diffusion tensor imaging (DTI) allows a live look into the microstructure of white matter in the brain and is an important complement to volumetric studies of specific structures such as the amygdala.

DTI may be particularly informative for the study of autism because it has been speculated that white matter (the connections between neurons) defects may be even more pronounced than gray matter defects for affected individuals. Furthermore, in contrast to gray matter, white matter volume continues to increase across childhood and adolescence, thus allowing for analyses of growth curves and changes specific to the microstructure of axons. (See papers by Courchesne, et al., 2000; Durston, et al., 2001; Giedd, et al., 1999) for more information about the development of white matter across development.

What is DTI?

Studies that utilize DTI technology generally describe two characteristics of white matter within a particular "voxel" in the brain:

the overall quantity of the diffusion of water molecules (often referred to as mean diffusivity)
the directionality of the diffusion of water molecules (often referred to as anisotropy)

Diffusion imaging takes advantage of the fact that the myelin sheath surrounding an axon restricts the diffusion of water perpendicular to the axon, while allowing relatively free diffusion of water parallel to the axon.

This partially restricted motion is referred to as anisotropic diffusion, and carries a theoretical maximum value of 1. In contrast, completely free diffusion of water, as is found in ventricles, is said to be isotropic and theoretical. FA values should be near zero.

Fractional Anisotropy (FA)

As a concept, fractional anisotropy (FA) is thought to reflect both the size and number of myelinated axons and the coherence of axonal orientation (Neil, et al., 1998). Thus, low FA values may suggest decreased fiber density, reduced myelination of fiber tracts or less directionally coherent organization of fibers within a voxel.

White matter injuries such as a stroke result in low FA values, and studies have shown a correlation between low FA values and reduced cognitive performance (Skranes, et al., 2007).

FA values also decrease as a consequence of healthy aging Kochunov, et al., 2007), and can be even more severely reduced in degenerative cases of aging such as Alzheimer's disease (Chua, Wen, Slavin, & Sachdev, 2008). In contrast, high FA values are thought to reflect coherently bundled, myelinated fibers oriented along the axis of greatest diffusion or a general increase in the size or number of myelinated axons within a particular voxel.

For an excellent review of how brain diffusion properties are affected in clinical samples, see (Cascio, Gerig, & Piven, 2007).

What Do DTI Studies Tell us About Autism?

Given an abnormal brain growth trajectory in autism, what profile of white matter microstructure, as characterized by diffusivity and FA values, would be predicted? During the first phase of brain growth in autism, namely the overgrowth phase, there is no clear prediction. That is, FA values could theoretically be either increased, reflecting greater number of axons and increased myelination, or decreased, reflecting poorly organized fiber tracts within cortex particularly in the frontal lobes.

In the only study to use DTI to examine white matter during a time period that coincides with early brain overgrowth, Ben Bashat et al. (2007) examined FA and diffusivity indices (displacement) in seven toddlers with confirmed autism ranging in age from 1.8 to 3 years. Contrasting DTI values were also obtained from a sample of over 40 typically developing infants and children.

Although the autism sample size was small, results were remarkably consistent - 100% of the toddlers with autism had FA values that exceeded the normal mean in some brain regions such as the forceps minor region (the anterior portion of the corpus callosum that extends into the frontal lobes). Region of interest analyses revealed that the largest FA increases were in the genu of the corpus callosum, posterior limb of the internal capsule and corticospinal tracts.

The authors interpret their findings as evidence of accelerated maturation of white matter in autism. Although it is only one study, results from Ben Bashat et al. (2007) suggest that FA values in particular may be increased during the overgrowth phase of brain development in autism.

Tractography

Advanced visualization of DTI data can be obtained via a method commonly referred to as "tractography" or "DTI fiber tracking." Fiber tracking uses the diffusion tensor of each voxel to follow an axonal tract in three dimensions from voxel to voxel through the human brain.

Because DTI provides only microstructural information at relatively low spatial resolution, DTI fiber tracking is often combined with functional and/or higher resolution anatomic information to delineate specific pathways. Currently there are no published tractography studies in infants and young children with autism.

The UCSD Autism Center of Excellence has studies under way to examine white matter structure in infants at risk for autism using both DTI and tractography. Tractography may be an excellent mechanism to visualize aberrant white matter tract projections in infants at risk for autism.