Axon diameter and intra-axonal volume fraction of the corticospinal tract in idiopathic normal pressure hydrocephalus measured by q-space imaging

Abstract

Purpose: Previous studies suggest that compression and stretching of the corticospinal tract (CST) potentially cause treatable gait disturbance in patients with idiopathic normal pressure hydrocephalus (iNPH). Measurement of axon diameter with diffusion MRI has recently been used to investigate microstructural alterations in neurological diseases. In this study, we investigated alterations in the axon diameter and intra-axonal fraction of the CST in iNPH by q-space imaging (QSI) analysis.

Methods: Nineteen patients with iNPH and 10 age-matched controls were recruited. QSI data were obtained with a 3-T system by using a single-shot echo planar imaging sequence with the diffusion gradient applied parallel to the antero-posterior axis. By using a two-component low-q fit model, the root mean square displacements of intra-axonal space ( = axon diameter) and intra-axonal volume fraction of the CST were calculated at the levels of the internal capsule and body of the lateral ventricle, respectively.

Results: Wilcoxon's rank-sum test revealed a significant increase in CST intra-axonal volume fraction at the paraventricular level in patients (p<0.001), whereas no significant difference was observed in the axon diameter. At the level of the internal capsule, neither axon diameter nor intra-axonal volume fraction differed significantly between the two groups.

Conclusion: Our results suggest that in patients with iNPH, the CST does not undergo irreversible axonal damage but is rather compressed and/or stretched owing to pressure from the enlarged ventricle. These analyses of axon diameter and intra-axonal fraction yield insights into microstructural alterations of the CST in iNPH.

Figure 1. Examples of the acquired diffusion weighted images.

Figure 2. Examples of axon diameter maps (top row) and intra-axonal volume fraction maps (middle row).

ROIs are shown in the raw diffusion image (bottom row, b = 2000 s/mm²).

Figure 3. Boxplot comparing the CST axon diameter and intra-axonal volume fraction between the controls and iNPH patients.

Statistical analyses revealed a significant increase in CST intra-axonal volume fraction at the paraventricular level in the patients, whereas no significant difference was observed in the axon diameter. At the level of the internal capsule, neither axon diameter nor intra-axonal volume fraction differed significantly between the two groups. * The significance level was set at p = 0.006 (Bonferroni's correction for multiple comparison).