Changes in glymphatic function after mild traumatic brain injury: findings from one and three-month
Poster No:
1915
Submission Type:
Abstract Submission
Authors:
Eunkyung Kim1, Han Gil Seo1, Roh-Eul Yoo1, Byung-Mo Oh1
Institutions:
1Seoul National University Hospital, Seoul, Republic of Korea
First Author:
Co-Author(s):
Introduction:
Changes in glymphatic function after mild traumatic brain injury (mTBI) have been recognized in recent studies [1, 2], particularly in its role in clearing metabolic waste in the brain. However, their longitudinal alterations remain poorly understood. This study investigated changes in glymphatic function in individuals with mTBI by assessing diffusion tensor imaging (DTI) at two timepoints: within one month and after three months post-injury.
Methods:
Thirty-nine individuals with mTBI (47.2±14.9y) and thirty-five healthy individuals (44.3±13.1y) underwent DTI and susceptibility-weighted imaging (SWI) using a 3-T Siemens scanner. To estimate diffusivity along the perivascular space (APLS) [3], DTI data were preprocessed to generate fractional anisotropy (FA) color maps thresholded at 0.2. SWI data was registered to the corresponding FA image. An axial slice was selected showing projection and association fibers at the level of the lateral ventricles and laterally running parenchymal vessels, by referencing the FA color map and SWI data. Two square regions of interest (ROIs), each measuring 4 voxels (3.8 mm sides), were manually drawn on the left projection and association fibers. Diffusivity values along the x-, y-, and z- axes were calculated within these ROIs.
The ALPS index was calculated as the ratio of the mean diffusivity in projection and association fibers (Dxx, proj, Dxx,asso) to the mean diffusivity in perpendicular directions (Dyy,proj, Dzz,assoc). FA image obtained three months post-injury were registered to those from one month. The inverse transformation matrix was applied to the ROIs to ensure consistent placement across timepoints, with slight manual adjustment due to head position. All ROIs in each timepoints were visually inspected to confirm proper localization.
Two-sample t-test was conducted to compare the ALPS index between groups. Paired sample t-test was conducted between the ALPS index acquired from different timepoint within the patient group. To assess changes across timepoints, the patient group was divided into good and poor prognosis subgroups based on the difference in ALPS index between three months and one month post-injury. The good prognosis subgroup had ALPST1 - ALPST0 > 0 while the poor prognosis subgroup had ALPST1 - ALPST0 < 0. Changes in clinical characteristics, including the Rivermead post-concussion symptoms questionnaire (RPCSQ), Beck depression inventory, Korean version of the Montreal cognitive assessment, Frontal assessment battery, and Glasgow outcome scale extended were compared between the subgroups using mixed-effects analysis of variance. Relationship between the changes in clinical characteristics and changes in ALPS index was also examined using correlation analyses.
The ALPS index was calculated as the ratio of the mean diffusivity in projection and association fibers (Dxx, proj, Dxx,asso) to the mean diffusivity in perpendicular directions (Dyy,proj, Dzz,assoc). FA image obtained three months post-injury were registered to those from one month. The inverse transformation matrix was applied to the ROIs to ensure consistent placement across timepoints, with slight manual adjustment due to head position. All ROIs in each timepoints were visually inspected to confirm proper localization.
Two-sample t-test was conducted to compare the ALPS index between groups. Paired sample t-test was conducted between the ALPS index acquired from different timepoint within the patient group. To assess changes across timepoints, the patient group was divided into good and poor prognosis subgroups based on the difference in ALPS index between three months and one month post-injury. The good prognosis subgroup had ALPST1 - ALPST0 > 0 while the poor prognosis subgroup had ALPST1 - ALPST0 < 0. Changes in clinical characteristics, including the Rivermead post-concussion symptoms questionnaire (RPCSQ), Beck depression inventory, Korean version of the Montreal cognitive assessment, Frontal assessment battery, and Glasgow outcome scale extended were compared between the subgroups using mixed-effects analysis of variance. Relationship between the changes in clinical characteristics and changes in ALPS index was also examined using correlation analyses.
Results:
The ALPS index obtained within a month after injury showed no significant difference compared to controls (p=0.162). However, the index measured at three months post-injury was significantly reduced (p=0.008) (Figure 1). Although the ALPS index decreased across timepoints, the reduction did not reach statistical significance (p=0.0732). Mixed-effect analysis of variance revealed a significant group effect (p<0.001), indicating that the poor prognosis group had significantly higher RPCSQ scores compared to the good prognosis group. However, there was no significant change in RPCSQ scores over time across both groups. A marginal trend of group by time interaction (p=0.092) suggested that the rate of changes in RPCSQ over time may differ between subgroups. The changes in RPCSQ had a negative relationship with change in ALPS index in good prognosis group, while the relationship was not observed in the poor prognosis group (Figure 2).
Conclusions:
The ALPS index showed significant reduction at three months post-injury, indicating potential glymphatic dysfunction over time. Correlations between changes in RPCSQ and ALPS index suggest differing recovery dynamics between the good and poor prognosis groups.
Modeling and Analysis Methods:
Other Methods 2
Novel Imaging Acquisition Methods:
Diffusion MRI 1
Keywords:
Trauma
Other - glymphatic function
1|2Indicates the priority used for review
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[2] Lian Li., et a., (2020). “MRI detection of impairment of glymphatic function in rat after mild traumatic brain injury” Brain research 1747: 147062
[3] Taoka, T., et al. (2017). "Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer’s disease cases." Japanese journal of radiology 35: 172-178
This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2018R1C1B6002554, 2021R1A2B5B02087294, and 2022R1C1C2006405), and was also supported by a grant from the MOLIT Research Fund (NTRH RF-2022006).