Altered glymphatic system in idiopathic normal pressure hydrocephalus

Objective: To assess the glymphatic activity in patients with idiopathic normal pressure hydrocephalus (NPH) using the "Diffusion Tensor Image-Analysis aLong the Perivascular Space (DTI-ALPS)" method, and determine the feasibility of non-invasive MRI for the evaluation of the glymphatic function. Methods: Between April 2017 and March 2019, 16 patients diagnosed with NPH and 16 ageand sex-matched controls were included. On 3T DTI-MRI, the diffusivities along x-, y-, and z-axes were measured, and the ALPS-index - a ratio that accentuated water diffusion along the perivascular space - was calculated by two independent readers. The inter-observer agreement was tested using the interclass correlation coefficient. The differences in the diffusivities and the ALPS-index between the NPH and control groups were compared using the Mann-Whitney test. The values were also compared according to the treatment response to the cerebrospinal fluid drainage and correlated with the callosal angle using a correlation coefficient. Results: The inter-observer agreements were excellent for the diffusivities and the ALPS-index. The diffusivity along the x-axis in the projection fibers area and the ALPS-index were significantly lower in patients with NPH (median, 0.556/1.181) than in the controls (0.610/1.540), respectively (P = 0.032/< 0.0001). The ALPS-index was significantly lower in the NPH group who did not show treatment response than those who showed symptomatic relief (0.987/1.329; P < 0.0001). The ALPS-index showed a significant positive correlation with the callosal angle (r = 0.82, P = 0.0001). Conclusions: The DTI-ALPS method can be a useful imaging tool for identifying glymphatic dysfunction and for individually quantifying glymphatic activity in patients with NPH.