Water diffusion-weighted MRI produces quantitative maps of microscopic displacement of water molecules that occur as part of the physical diffusion process. This is achieved by sensitizing the magnetic resonance signal to the random motion of water molecules by using strong magnetic field gradients. By varying the magnetic field gradient, one can obtain different degrees of diffusion-weighted images and calculate an apparent diffusion coefficient (ADC) for each voxel (5).
Since diffusion of water molecules is highly sensitive to microstructural changes in the cerebral tissue, diffusion-weighted MRI has become a firmly established method to probe the functional integrity of brain tissue, especially in acute cerebral ischemia (29). Diffusion-weighted MRI has a high sensitivity to detect structural abnormalities. However, it is important to bear in mind that diffusion-weighted MRI has a low specificity in terms of underlying pathophysiology since various mechanisms (e.g., edema, neurotoxicity, Wallerian degeneration) can affect the diffusion process in the cerebral tissue.
Three studies have characterized water diffusion in patients with atypical parkinsonian disorders. Patients with PSP showed an increase in ADCs in the prefrontal and precentral white matter (30) and the basal ganglia (31,32). An increase in ADCs was also found in patients with the MSA-P variant of MSA (32), but not in patients with PD (31,32). These data indicate that diffusion-weighted imaging may help to distinguish between PD and atypical parkinsonian disorders, but fails to discriminate between PSP and MSA.
The microstructure of the brain tissue imposes directional constraints to the diffusion of water molecules in the brain (referred to as anisotropy). Diffusion is particularly anisotropic in white matter tracts because water preferentially diffuses along the direction of white matter fibres. Anisotropic diffusion is more adequately characterized by a diffusion tensor. A diffusion tensor is an array of nine coefficients that fully characterizes the directional properties of water diffusion in space.
Diffusion tensor-encoded MRI (DT-MRI) uses different gradient orientations to characterize the diffusion tensor in each voxel of the brain (5). The diffusion tensor is often displayed as an elipsoid (5). The average size of the ellipsoid represents the overall displacement of the water molecules in a given voxel (mean diffusivity). The eccentricity of the ellipsoid characterizes the degree of anisot-ropy. A sphere indicates isotropic diffusion whereas an elongated (cigar-shaped) or flat (pancake-shaped) ellipsoid indicates anisotropic diffusion. The main axis of the ellipsoid corresponds to the preferential direction of diffusion.
In the white matter, the main axis of the diffusion tensor is thought to represent the prevailing orientation of white matter bundles in each voxel. DT-MRI allows one to track white matter fibers by connecting neighboring voxels on the basis of their main direction of the diffusion tensor (i.e., main fiber orientation) (33). Anisotropy measurements can be used to identify subtle abnormalities in the organization of white matter tracks that are not evident with plain, anatomical MRI (34). However, it is worth bearing in mind that currently available DT-MRI techniques can only visualize white matter bundles that consist of a large number of axons, limiting fiber tracking to the white matter. Furthermore, DT-MRI can not probe the directional and functional status of the information flow along the white matter tracts. DT-MRI also has a considerable potential for functional mapping of subcortical gray matter. A recent study employed DT-MRI to differentiate the nuclei in the thalamus and to map their connectivity (35).
Because DT-MRI provides a unique approach to tracking anatomical connectivity in vivo, DT-MRI can provide important new insights into the neuroanatomical basis of atypical parkinsonian disorders linking clinical symptoms with impaired anatomical connectivity. Though no DT-MRI study has been published on atypical parkinsonian disorders at this stage, it is safe to state that DT-MRI provides a promising tool to pinpoint characteristic patterns of abnormal connectivity, especially in CBD and MSA. This may be used to separate atypical parkinsonian disorders from PD.
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