Age-dependent changes in glymphatic system function in human brain using non-invasive MRI methods.
Poster No:
2607
Submission Type:
Abstract Submission
Authors:
Weiwei Zhao1, Tianxin Mao1, Hengyi Rao1
Institutions:
1Center for Magnetic Resonance Imaging Research, Shanghai International Studies University, Shanghai, China
First Author:
Weiwei Zhao
Center for Magnetic Resonance Imaging Research, Shanghai International Studies University
Shanghai, China
Center for Magnetic Resonance Imaging Research, Shanghai International Studies University
Shanghai, China
Co-Author(s):
Tianxin Mao
Center for Magnetic Resonance Imaging Research, Shanghai International Studies University
Shanghai, China
Center for Magnetic Resonance Imaging Research, Shanghai International Studies University
Shanghai, China
Hengyi Rao
Center for Magnetic Resonance Imaging Research, Shanghai International Studies University
Shanghai, China
Center for Magnetic Resonance Imaging Research, Shanghai International Studies University
Shanghai, China
Introduction:
The glymphatic system (GS)1 facilitates the exchange of cerebrospinal fluid (CSF) and brain interstitial fluid (ISF), resulting in the movement of fluid across the brain parenchyma to eliminate metabolic waste products2. The abnormal accumulation of this waste is a common feature in most neurodegenerative diseases3. Therefore, understanding the age-dependent trajectory of GS clearance function is crucial for comprehending brain aging and predicting neurodegenerative diseases. While interest in studying the GS in humans has markedly increased in the last decade, current approaches involving intrathecal gadolinium are challenging for research purposes and unsuitable for repeated measurements to assess changes in glymphatic transport across various physiological states. In this context, we discuss two potential non-invasive MRI methods for investigating the GS and its association with aging.
Methods:
Forty-five healthy adults (23 females, mean age = 37.43 ± 10.29 years) participated in this study4. These participants were categorized into three groups with 10-year intervals (21-30, 31-40, 41-50), referred to as the 20s group, 30s group, and 40s group. Each participant underwent two MRI scans at the same time on two mornings. The imaging protocol included high-resolution T1-weighted anatomic imaging, resting-state functional MRI (rfMRI), and diffusion tensor imaging (DTI), all conducted using a 3T Siemens Trio system (Siemens Medical Systems, Erlangen, Germany) (for detailed MRI scan parameters, see4).
The rfMRI data was pre-processed by SPM 12, where nuisance regressions of global signal, CSF signal, and motion parameters were omitted5,6. Consistent with prior studies5,7, the cross-correlation between the gBOLD signal and CSF signal was calculated for each participant. The maximal anticorrelation was employed to quantify the strength of gBOLD-CSF coupling.
The DTI images were pre-processed by FSL. The fractional anisotropy map of each subject was registered to the JHU-ICBM-FA template. The identification of the superior corona radiata (SCR) and the superior longitudinal fasciculus (SLF) as projection and association fibers at the lateral ventricle body level was based on the JHU-ICBM-DTI-81-white-matter Labeled Atlas. The diffusivity values of Dxx, Dyy, and Dzz of bilateral SLF and SCR were extracted, and the ALPS index was calculated using the following formula8: DTI-ALPS index = mean(Dxproj,Dxassoc)/mean(Dyproj,Dzassoc)
The rfMRI data was pre-processed by SPM 12, where nuisance regressions of global signal, CSF signal, and motion parameters were omitted5,6. Consistent with prior studies5,7, the cross-correlation between the gBOLD signal and CSF signal was calculated for each participant. The maximal anticorrelation was employed to quantify the strength of gBOLD-CSF coupling.
The DTI images were pre-processed by FSL. The fractional anisotropy map of each subject was registered to the JHU-ICBM-FA template. The identification of the superior corona radiata (SCR) and the superior longitudinal fasciculus (SLF) as projection and association fibers at the lateral ventricle body level was based on the JHU-ICBM-DTI-81-white-matter Labeled Atlas. The diffusivity values of Dxx, Dyy, and Dzz of bilateral SLF and SCR were extracted, and the ALPS index was calculated using the following formula8: DTI-ALPS index = mean(Dxproj,Dxassoc)/mean(Dyproj,Dzassoc)
Results:
In the 40s age group, the gBOLD-CSF coupling (-0.31±0.10) exhibited a significantly weaker connection compared to both the 20s (-0.35±0.11, p = 0.044) and 30s (-0.39±0.10, p = 0.002) groups (Figure 1). Although a linear correlation trend was observed between gBOLD-CSF coupling and age, the p-value did not reach statistical significance (p = 0.142).
The ALPS index demonstrated a significant decrease in the 30s group (1.29±0.12) compared to both the 20s (1.39±0.12, p < 0.001) and 40s groups (1.38±0.11, p = 0.002). A quadratic relationship was observed between the ALPS index and age (R2 = 0.112, p = 0.001). The graphical representation of ALPS index versus age revealed a U-shaped pattern, reaching its nadir at 35 years of age, followed by an increase from approximately 40 years of age (Figure 2).
The ALPS index demonstrated a significant decrease in the 30s group (1.29±0.12) compared to both the 20s (1.39±0.12, p < 0.001) and 40s groups (1.38±0.11, p = 0.002). A quadratic relationship was observed between the ALPS index and age (R2 = 0.112, p = 0.001). The graphical representation of ALPS index versus age revealed a U-shaped pattern, reaching its nadir at 35 years of age, followed by an increase from approximately 40 years of age (Figure 2).
·Fig 1. The results of age against gBOLD-CSF coupling.
·Fig 2. The results of age against ALPS index.
Conclusions:
Two brain imaging modalities, rfMRI and DTI, were employed to assess their sensitivity to age-related changes in fluid transport. The gBOLD-CSF coupling and ALPS index were utilized to depict the clearance function of the GS from distinct perspectives, with the ALPS index revealing a U-shaped pattern in relation to age. Given the clinically relevant associations linking aging, glymphatic transport, and neurological disorders, both methodologies present an attractive avenue for gaining profound insights into the intricate interplay among vascular and CSF circulation, as well as ISF solute transport. These insights are crucial for future investigations pertaining to neurological diseases, cognitive function, or as reference values.
Lifespan Development:
Aging 2
Lifespan Development Other
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Normal Development
Novel Imaging Acquisition Methods:
Multi-Modal Imaging
Physiology, Metabolism and Neurotransmission :
Cerebral Metabolism and Hemodynamics 1
Keywords:
Aging
Cerebro Spinal Fluid (CSF)
MRI
Other - Neuro-fluids; Glymphatic system; Brain clearance
1|2Indicates the priority used for review
Provide references using author date format
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