Structural Bias on the Assessment of Periventricular Flow as Revealed by Post-mortem Human Brain
Presented During:
Friday, June 27, 2025: 11:30 AM - 12:45 PM
Brisbane Convention & Exhibition Centre
Room:
M4 (Mezzanine Level)
Poster No:
1916
Submission Type:
Abstract Submission
Authors:
Sihui Li1, Ruike Chen1, Zuozhen Cao1, Qinfeng Zhu1, Yihan Ma1, Keqing Zhu1, Zixuan Lin1, Dan Wu1
Institutions:
1Zhejiang University, Hangzhou, Zhejiang
First Author:
Co-Author(s):
Introduction:
Diffusion tensor image analysis along the perivascular space (DTI-ALPS) has emerged to evaluate glymphatic function in Alzheimer's disease (Taoka, 2020). However, the underlying mechanism for ALPS change remains controversial(Wright et al., 2023; Taoka et al., 2024). With the post-mortem brains DTI with autopsy-confirmed AD change, we aim to explore and correct the structural bias on the ALPS index.
Methods:
Theory: ALPS=mean(Dxproj,Dxassoc/mean(Dyproj,Dzassoc)(Taoka et al., 2017). The ratio Dxproj/Dyproj and Dxassoc/Dzassoc represent the asymmetry between the diffusivity components on the transverse and the perpendicular fiber direction (Figure 1a), thus was referred as projection and association asymmetry. We hypothesize (Figure 1b) that the asymmetry is influenced by the total movement including flowing fluid and restricted diffusion along WM tracts. In post-mortem brains, the asymmetry reflects pure structural component as no glymphatic activity presents, which provides information to correct the structural bias for the in-vivo ALPS.
ALPS in post-mortem: 9 Aβ+ and 9 Aβ- post-mortem human brain samples were obtained (Figure 1c). Diffusion MRI was acquired on a 7T MRI scanner (Siemens Healthcare). The 3D high-angular resolution diffusion MRI was performed at 0.8 isotropic resolution with 60 diffusion directions. B-value of 6000 mm/s2was used considering lower diffusivity in specimens(Roebroeck, Miller and Aggarwal, 2019). Diffusivity maps and color-coded fractional anisotropy maps were calculated using MRtrix(Tournier et al., 2019). The ROIs were manually delineated at the location where the direction of the deep medullary veins was perpendicular to the ventricular body.
Corrected ALPS (c-ALPS): c-ALPS was proposed as mean(Dxproj,Dxassoc)/mean(aDyproj,bDzassoc) where a and b are the constant derived from the projection and association asymmetry in the post-mortem brains. c-ALPS index equals 1 in post-mortem data, consistent with the fact that no glymphatic activity is presented in post-mortem brains. For in-vivo brain where glymphatic flow exists, the correction formula yields an index higher than 1.
Application: 110 ADNI participants were included(Figure 1d). AD status was predefined by Aβ PET SUVR. An automatic approach(Liu et al., 2024) was utilized to delineated ROIs to calculate ALPS and c-ALPS for AD-related analysis.
ALPS in post-mortem: 9 Aβ+ and 9 Aβ- post-mortem human brain samples were obtained (Figure 1c). Diffusion MRI was acquired on a 7T MRI scanner (Siemens Healthcare). The 3D high-angular resolution diffusion MRI was performed at 0.8 isotropic resolution with 60 diffusion directions. B-value of 6000 mm/s2was used considering lower diffusivity in specimens(Roebroeck, Miller and Aggarwal, 2019). Diffusivity maps and color-coded fractional anisotropy maps were calculated using MRtrix(Tournier et al., 2019). The ROIs were manually delineated at the location where the direction of the deep medullary veins was perpendicular to the ventricular body.
Corrected ALPS (c-ALPS): c-ALPS was proposed as mean(Dxproj,Dxassoc)/mean(aDyproj,bDzassoc) where a and b are the constant derived from the projection and association asymmetry in the post-mortem brains. c-ALPS index equals 1 in post-mortem data, consistent with the fact that no glymphatic activity is presented in post-mortem brains. For in-vivo brain where glymphatic flow exists, the correction formula yields an index higher than 1.
Application: 110 ADNI participants were included(Figure 1d). AD status was predefined by Aβ PET SUVR. An automatic approach(Liu et al., 2024) was utilized to delineated ROIs to calculate ALPS and c-ALPS for AD-related analysis.
Results:
Asymmetry in post-mortem brains varies on the Aβ status and age (Figure 2a&b)
ALPS and projection asymmetry was significantly lower in the Aβ+ group even when there was no glymphatic flow (p=0.044 and p = 0.045). The correction index a was estimated by its mean values in Aβ+ and Aβ- subjects. In association area, structural asymmetry showed a negative correlation with age (p=0.044). The correction index b was fitted by linear regression analysis with the slope=-0.0033 (p=0.044).
c-ALPS showed weaker results in AD-related analysis
Reduced ALPS but no significant difference of the c-ALPS was observed when comparing Aβ+ to Aβ- group (Figure 2c). The ALPS significantly correlated with AD-related indicators. The c-ALPS index's correlation with AV45 PET SUVR became non-significant (Figure 2d).
ALPS and projection asymmetry was significantly lower in the Aβ+ group even when there was no glymphatic flow (p=0.044 and p = 0.045). The correction index a was estimated by its mean values in Aβ+ and Aβ- subjects. In association area, structural asymmetry showed a negative correlation with age (p=0.044). The correction index b was fitted by linear regression analysis with the slope=-0.0033 (p=0.044).
c-ALPS showed weaker results in AD-related analysis
Reduced ALPS but no significant difference of the c-ALPS was observed when comparing Aβ+ to Aβ- group (Figure 2c). The ALPS significantly correlated with AD-related indicators. The c-ALPS index's correlation with AV45 PET SUVR became non-significant (Figure 2d).
Conclusions:
The study explored ALPS in post-mortem AD brains from the perspective of structural bias. c-ALPS index showed weaker results in AD-related analysis, indicating the original index was influenced by structural asymmetry of fibers. Changes in fiber architecture, like structural asymmetry may serve as useful biomarkers for AD, but should not be conflated with glymphatic function. The underlying mechanism of ALPS alteration, whether the structure or physiology matters, should be interpreted cautiously.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 2
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Other Methods
Novel Imaging Acquisition Methods:
Diffusion MRI 1
Keywords:
Aging
MRI
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - post-mortem human brain;glymphatic;
1|2Indicates the priority used for review
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Provide references using APA citation style.
Roebroeck, A., Miller, K.L. and Aggarwal, M. (2019) ‘Ex vivo diffusion MRI of the human brain: Technical challenges and recent advances’, NMR in Biomedicine, 32(4), pp. 1–14.
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(4), pp. 172–178.
Taoka, T. et al. (2024) ‘Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS): Revisiting the Meaning and Significance of the Method’, Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine, 23(3), pp. 268–290.
Taoka, T. and Naganawa, S. (2020) ‘Neurofluid Dynamics and the Glymphatic System : A Neuroimaging Perspective’, Korean Journal of Radiology, 21(11), pp. 1199–1209.
Tournier, J.D. et al. (2019) ‘MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation’, NeuroImage, 202(August), p. 116137.
Wright, A.M. et al. (2023) ‘Exploring Radial Asymmetry in MR Diffusion Tensor Imaging and Its Impact on the Interpretation of Glymphatic Mechanisms’, Journal of Magnetic Resonance Imaging, 60(4), pp. 1432–1441.