Supplemental tables for: A periventricular gradient of innate immune cell activation in Multiple Sclerosis

Objectives: To explore in-vivo innate immune
cell activation as a function of the distance from ventricular CSF in
patients with Multiple Sclerosis (MS) using [18F]-DPA714 PET, and to
investigate its relationship with periventricular microstructural damage,
evaluated by magnetization transfer ratio (MTR), and with trajectories of
disability worsening. Methods: Thirty-seven MS patients and
nineteen healthy controls underwent MRI and [18F]-DPA714 TSPO
dynamic PET, from which individual maps of voxels characterized by innate
immune cell activation (DPA+) were generated. White matter (WM) was
divided in 3mm-thick concentric rings radiating from the ventricular
surface toward the cortex, and the percentage of DPA+ voxels and mean MTR
were extracted from each ring. Two-year trajectories of disability
worsening were collected to identify patients with and without recent
disability worsening. Results: The percentage of DPA+ voxels was
higher in patients compared to controls in the periventricular WM
(p=6.10e-6), and declined with increasing distance from ventricular
surface, with a steeper gradient in patients compared to controls
(p=0.001). This gradient was found both in periventricular lesions and
normal-appearing WM. In the total WM, it correlated with a gradient of
microstructural tissue damage measured by MTR (rs=-0.65,
p=1.0e-3). When compared to clinically stable
patients, patients with disability worsening were
characterized by a higher percentage of DPA+ voxels in
the periventricular normal-appearing WM (p=0.025).
Conclusions: Our results demonstrate that in MS the innate immune
cell activation predominates in periventricular regions and associates
with microstructural damage and disability worsening. This could result
from the diffusion of pro-inflammatory CSF-derived factors into
surrounding tissues.