Diffusion tensor imaging profiles reveal specific neural tract distortion in normal pressure hydrocephalus

Abstract

Background: The pathogenesis of normal pressure hydrocephalus (NPH) remains unclear which limits both early diagnosis and prognostication. The responsiveness to intervention of differing, complex and concurrent injury patterns on imaging have not been well-characterized. We used diffusion tensor imaging (DTI) to explore the topography and reversibility of white matter injury in NPH pre- and early after shunting.

Methods: Twenty-five participants (sixteen NPH patients and nine healthy controls) underwent DTI, pre-operatively and at two weeks post-intervention in patients. We interrogated 40 datasets to generate a full panel of DTI measures and corroborated findings with plots of isotropy (p) vs. anisotropy (q).

Results: Concurrent examination of DTI measures revealed distinct profiles for NPH patients vs. controls. PQ plots demonstrated that patterns of injury occupied discrete white matter districts. DTI profiles for different white matter tracts showed changes consistent with i) predominant transependymal diffusion with stretch/ compression, ii) oedema with or without stretch/ compression and iii) predominant stretch/ compression. Findings were specific to individual tracts and dependent upon their proximity to the ventricles. At two weeks post-intervention, there was a 6·7% drop in axial diffusivity (p = 0·022) in the posterior limb of the internal capsule, compatible with improvement in stretch/ compression, that preceded any discernible changes in clinical outcome. On PQ plots, the trajectories of the posterior limb of the internal capsule and inferior longitudinal fasciculus suggested attempted 'round trips'. i.e. return to normality.

Conclusion: DTI profiling with p:q correlation may offer a non-invasive biomarker of the characteristics of potentially reversible white matter injury.

Fig 1. Illustration of white matter regions of interest (ROIs).

White matter tracts represented in the context of normal ventricular size for clarity.

Fig 2. DTI profiles in pre-operative and post-operative NPH patients vs. healthy controls (in percentage difference (%)).

Illustration of DTI profiles—Four measures comprising the full panel for DTI interpretation, (FA, MD, L1 and L2and3), are visually represented as radar graphs. Differences in measures may be viewed concurrently; each axis is scalar and dimensionally comparable. The morphology of the graph, i.e. the shape of the radar web, is dependent upon i) the degree of differences between the two groups compared (the larger the differences, the bigger the area of the radar web) and ii) the DTI measure predominantly affected (the radar web points towards the DTI measure with the highest percentage difference between the groups).

Fig 3. PQ plots of pre-operative and post-operative NPH patients compared to healthy controls.

The effect of shunting in NPH patients. Trajectories of six brain ROIs in the p:q plane, illustrating their evolution from control (HEALTHY), to hydrocephalus pre-shunting (PRE) and two weeks after shunting (POST). A round trip would represent that the ROIs have completed a return journey to normal diffusion levels.