Diffusion Weighted Imaging and Diffusion Tensor Imaging of White Matter Diseases In Children

Julie H. Harreld and Zoltan Patay

Key Points

  • Though patterns of T2 signal abnormality may be diagnostic for some pediatric white matter disorders, many are nonspecific in appearance on conventional imaging.
  • Vasogenic edema, cytotoxic edema, myelin edema, myelin vacuolation, and white matter rarefaction all increase brain water content and cause increased signal onT2-weighted imaging.
  • Diffusion weighted imaging and diffusion metrics, such as apparent diffusion coefficient and fractional anisotropy, can distinguish between these entities and improve magnetic resonance imaging-based differential diagnosis of pediatric white matter diseases, and also provide clues to stage/activity of disease and underlying pathology.


In diffusion imaging, directional diffusion gradients are applied to a T2-weighted (spin-echo) echo-planar imaging (EPI) sequence before and after a 180-degree refocusing pulse. Water protons moving freely through these gradients acquire random spins and are thus dephased, causing signal loss in voxels where water motion (diffusion) is significant. Conversely, stationary or slowly moving protons generate increased signal on diffusion weighted images (DWIs). The apparent diffusion coefficient (ADC) may be calculated from images acquired without and with a diffusion gradient and allows quantitation of the displacement of water molecules over time (mm2/s) in a particular voxel.1'2

In tissues, water mobility may be restricted by cell membranes, macromolecules, or decreased extracellular spaces. In such cases, the signal on DWI is increased, and the ADC is decreased. For example, tissues with high cell density, such as small, round blue cell tumors like medulloblastoma and lymphoma, have decreased or “restricted” water diffusion and therefore appear bright on DWI. Hypercellularity due to a regional influx of cells, such as macrophages or glia, may also cause restricted diffusion (decreased ADC) and high signal on DWI. Cellular swelling due to cytotoxic edema, as in cerebral ischemia, also results in restricted diffusion due to resultant decreases in extracellular freely mobile water. Shift of water into the myelin sheath from the extracellular space, as occurs in intramyelinic edema or myelin vacuolation, may cause restricted diffusion in a similar or related fashion.3 This is in contrast to vasogenic edema, in which there is an accumulation of extracellular water due to blood-brain barrier (BBB) breakdown or osmotic shifts, causing increased ADC.4 Though all types of white matter edema may appear bright on T2-weighted imaging, ADC is increased in vasogenic edema (peritu- moral edema, infection/inflammation), but decreased in cytotoxic edema (affecting oligodendrocytes and astrocytes) or intramyelinic edema, permitting differentiation. However, different types of edema may coexist (see “maple syrup urine disease” later in this chapter) and even shift during the course of disease. By providing insight into the dominant edema type, diffusion imaging may help characterize dynamic white matter disease processes.

Although diffusion is apparently equal in all directions (isotropic) in gray matter, in white matter it is greatest parallel to the fiber bundles (“tracts”) and restricted perpendicular to the tracts, a property known as anisotropy. This is exploited in diffusion tensor imaging (DTI) and fiber tracking, and may be quantified as fractional anisotropy (FA), a measure of the propensity of water to diffuse in a single direction (e.g., along a white matter tract). An FA of 0 indicates isotropic diffusion, and the maximal FA of 1 indicates perfectly linear, anisotropic diffusion along the primary (longitudinal) eigenvector, which indicates axonal orientation. The mean of the second and third eigenvectors, which are perpendicular to the axon, is known as radial diffusivity and can provide further quantitation of myelin integrity. These metrics offer exciting, noninvasive, and reproducible approaches to qualitative and quantitative evaluation of white matter diseases.

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