Researchers at Butler Hospital Memory & Aging Program using diffusion-tensor imaging (DTI) to study white matter in the brain

Dr. Salloway’s research team is using a new MRI technique called diffusion-tensor imaging (DTI) to explore the relationship between the health of white matter (see below) in the brain and cognitive function (or thinking abilities) and behavior. We are studying these relationships in patients with mild cognitive impairment, Alzheimer’s disease, small blood vessel disease in the brain, and CADASIL (an inherited form of vascular dementia), and in cognitively-normal elderly control subjects. These projects are supported by funds from the National Institute of Mental Health, the Alzheimer’s Association, and the Brown University Center for Translational Brain Research. We are working closely with David H. Laidlaw, Ph.D. Associate Professor of Computer Science at Brown, an internationally recognized expert in DTI. It is our hope that this research will eventually help to identify individuals at greatest risk for developing Alzheimer’s disease and other disorders that cause dementia.

White matter lies below the surface of the brain and is comprised of fibers that connect brain cells in different brain regions. White matter gets its name from the fatty covering of the fibers, which give it a whitish appearance. The white matter fibers connect different brain regions together in coordinated networks. Several disorders can cause damage to white matter, including disease of the small blood vessels, multiple sclerosis, HIV infection, and others. Damage to white matter tracts, can cause cognitive or behavioral abnormalities due to disruption of brain networks. Figure 1 shows white matter on a brain section. Figure 2 shows an MRI with regions of white matter damage.

Figure 1: Photograph of an actual brain slice. Lighter colored areas are white matter (from: Haines, DE 2004. Neuroanatomy: An atlas of structures, sections, and systems, 6th edition. Baltimore: Lippincott, Williams, & Wilkins.)

 

 

Figure 2: MRI scan showing areas of damaged white matter (bright spots) presumably due to small blood vessel disease. The curved dark areas on the center are the ventricles, the fluid –filled cavities of the brain.

Conventional MRI scans provide only relatively large-scale (macroscopic) information about white matter damage but does not provide information about the microstructural integrity of the fiber tracts.

Diffusion-tensor imaging (DTI) represents a significant advance over conventional MRI in terms of measuring the health of white matter. DTI allows us to measure the microstructural integrity of white matter tracts in three dimensions. DTI data can be used to display white matter tracts including the twists and turns that these tracts take along their route. Some examples are provided below.

Figure 3: A) Conventional MRI image (T2-weighted image). Note that white matter is difficult to visualize. Water in the ventricles appear bright in this type of MRI image. B) DTI image (fractional anisotropy image). The bright areas represent regions of restricted water motion that correspond to white matter tracts. Dark areas in image B represent areas where water motion is not restricted in a particular direction and correspond to grey matter and ventricles (http://www.indyrad.iupui.edu/public/tili/)

Figure 4: Color-coded image of figure 3b showing the direction of white matter fibers. Green fibers are oriented vertically, red fibers are oriented left-to-right, blue fibers are oriented perpendicular to the screen. (http://www.indyrad.iupui.edu/public/tili/)

 

 

Figure 5 Left: Artists rendering of the brain sliced down the center. The corpus callosum, a large white matter structure that connects the right and left sides of the brain is seen in light green (http://temagami.carleton.ca/49.663/first.htm).

 

 

Right: Digital image of the corpus callosum based on DTI data and color-coded.

 

 

Several studies have now shown that DTI can detect abnormalities in white matter regions that appear normal on conventional MRI scans (Figure 4). This result has been shown in patients with small blood vessel disease and in patients with Alzheimer’s disease and in other brain disorders that cause dementia. In one recent study, DTI abnormalities in normal appearing white matter were associated with impairment on tests of planning and problem solving. These are important research findings because it suggests that DTI provides a much more sensitive measure of the health of white matter than does conventional MRI and that these subtle changes have an adverse effect on cognitive functioning.

DTI is performed using the same types of MRI scanners used for conventional MRI and its risks are not greater than those of conventional MRI. DTI measures white matter indirectly. In actuality, it measures the movement of water molecules in the brain. In white matter, water molecules move more freely along the length of the fibers but not across the fibers. This is mainly due to the fatty covering of the white matter fibers. DTI can detect these differences in the direction and amount of water movement in the brain. Water moves about more freely in damaged white matter than in healthy white matter. Thus, information about the movement of water in white matter provides an indirect measure of its health.

Research with DTI is still new, and a great deal of work is being done to develop methods for analyzing and visualizing this data. Researchers are exploring the utility of DTI for investigating white matter health in childhood disorders, brain tumors, stroke, head injury, HIV infection, multiple sclerosis, and other disorders. DTI appears to hold promise for identifying early and subtle changes in white matter integrity. In the future, DTI might help identify patients who should be targeted for more aggressive treatments of conditions such as high blood pressure that can affect the health of blood vessels and lead to white matter damage.