The factors associated with glymphatic system markers
Poster No:
1298
Submission Type:
Abstract Submission
Authors:
Yi-Chia Wei1, Chih‑Chin Hsu2, Lin Ching-Po3
Institutions:
1Chang Gung Memorial Hospital, Keelung City, Taiwan, 2National Yang Ming Chiao Tung University, Taipei, Taiwan, 3Department of Education and Research, Taipei City Hospital, Taipei, Taiwan
First Author:
Co-Author(s):
Introduction:
The glymphatic system is the water metabolism system that maintains waste clearance, nutrition, and volume transmission in the brain parenchyma. Several physiological factors have been noticed to affect fluid flow in the glymphatic system. However, a comprehensive analysis of factors affecting glymphatic activity is needed, as previous studies focused on individual factors. To address this, we conduct brain MRI scans and blood tests for the astrocyte biomarker glial fibrillary acidic protein (GFAP) to identify correlations with glymphatic activity.
Methods:
The older adult aged between 60-80 years old were enrolled from the Northeastern Taiwan Community Medicine Research Cohort (NTCMRC; ClinicalTrials.gov identifier NCT04839796). MRI scans were performed using a Siemens 3T Skyra MR scanner with high-resolution T1-weighted image (T1w) and diffusion-weighted images (DWI). We use the iDIO pipeline (Hsu, Chong et al. 2022) for DWI and T1w image preprocessing.
The diffusivity along the perivascular space (DTI-ALPS) index estimates the glymphatic flow along the medullary veins besides the lateral ventricle of the left cerebral hemisphere (Taoka, Masutani et al. 2017). The definition of DTI-ALPS index is the ratio of the mean of the x-axis diffusivity in the area of projection fibers (Dxproj) and x-axis diffusivity in the area of the association fibers (Dxassoc) divided by the mean of the y-axis diffusivity in the area of projection fibers (Dyproj) and the z-axis diffusivity of the association fibers (Dzassoc).
To evaluate the stagnation of interstitial fluid (ISF) drainage, the single-shell free water (FW) algorithm (Pasternak, Maier-Hein et al. 2014) was employed and executed using DIPY software (https://dipy.org). This method adhered to the principle proposed by Pasternak (2009) (Pasternak, Sochen et al. 2009), utilizing a selecting Euclidean metric with the canonical tensor representation for the feature metric (https://github.com/sameerd/DiffusionTensorImaging). A mask with FA > 0.2 was used to define the white matter mask of the brain. The mean volume fraction of FW for participants was then calculated by averaging the fraction values of each voxel within the white matter mask.
Immunomagnetic reduction (IMR) can detect trace amounts of molecules at a 10 pg/mL level in human plasma using antibody-coated magnetic nanoparticles. A semi-conductor magnetometer measures the magnetic susceptibility to quantify the target protein concentration, offering a low limit of detection for neurodegenerative proteins in human blood (Wei, Hsu et al. 2023).
The diffusivity along the perivascular space (DTI-ALPS) index estimates the glymphatic flow along the medullary veins besides the lateral ventricle of the left cerebral hemisphere (Taoka, Masutani et al. 2017). The definition of DTI-ALPS index is the ratio of the mean of the x-axis diffusivity in the area of projection fibers (Dxproj) and x-axis diffusivity in the area of the association fibers (Dxassoc) divided by the mean of the y-axis diffusivity in the area of projection fibers (Dyproj) and the z-axis diffusivity of the association fibers (Dzassoc).
To evaluate the stagnation of interstitial fluid (ISF) drainage, the single-shell free water (FW) algorithm (Pasternak, Maier-Hein et al. 2014) was employed and executed using DIPY software (https://dipy.org). This method adhered to the principle proposed by Pasternak (2009) (Pasternak, Sochen et al. 2009), utilizing a selecting Euclidean metric with the canonical tensor representation for the feature metric (https://github.com/sameerd/DiffusionTensorImaging). A mask with FA > 0.2 was used to define the white matter mask of the brain. The mean volume fraction of FW for participants was then calculated by averaging the fraction values of each voxel within the white matter mask.
Immunomagnetic reduction (IMR) can detect trace amounts of molecules at a 10 pg/mL level in human plasma using antibody-coated magnetic nanoparticles. A semi-conductor magnetometer measures the magnetic susceptibility to quantify the target protein concentration, offering a low limit of detection for neurodegenerative proteins in human blood (Wei, Hsu et al. 2023).
Results:
The study finally enrolled 71 participants from the initial screening of 86 participants (Figure 1).
The DTI-ALPS index is influenced by age and sex, smoking, VLDL, triglycerides, diabetes (DM), high fasting blood sugar, HbA1c, BMI, waist/calf circumference, and metabolic syndrome (MetS). Protective factors include total cholesterol and HDL.
The whole brain FW fraction, representing interstitial fluid transport correlates with age, sex, smoking, DM, fasting blood sugar, HbA1c, BMI, waist/calf circumference, and MetS. Higher systolic blood pressure (SBP) and hypertension correlate with higher FW fraction. Longer REM sleep and a higher REM ratio, but lower NREM/REM ratio, are linked to FW fraction.
Plasma GFAP correlates positively with age and is inversely associated with education and higher blood vitamin B12 levels. Chronic kidney disease and REM sleep elevates plasma GFAP.
Glymphatic markers are linked to cognitive performance. The DTI-ALPS index is associated with the digit-symbol substitution test (DSST) for psychomotor speed and the facial memory test (FMT). Similarly, FW fraction correlates with FMT. In contrast, plasma GFAP is associated with global cognition (MoCA, ADAS-cog, and DSST). (Figure 2)
The DTI-ALPS index is influenced by age and sex, smoking, VLDL, triglycerides, diabetes (DM), high fasting blood sugar, HbA1c, BMI, waist/calf circumference, and metabolic syndrome (MetS). Protective factors include total cholesterol and HDL.
The whole brain FW fraction, representing interstitial fluid transport correlates with age, sex, smoking, DM, fasting blood sugar, HbA1c, BMI, waist/calf circumference, and MetS. Higher systolic blood pressure (SBP) and hypertension correlate with higher FW fraction. Longer REM sleep and a higher REM ratio, but lower NREM/REM ratio, are linked to FW fraction.
Plasma GFAP correlates positively with age and is inversely associated with education and higher blood vitamin B12 levels. Chronic kidney disease and REM sleep elevates plasma GFAP.
Glymphatic markers are linked to cognitive performance. The DTI-ALPS index is associated with the digit-symbol substitution test (DSST) for psychomotor speed and the facial memory test (FMT). Similarly, FW fraction correlates with FMT. In contrast, plasma GFAP is associated with global cognition (MoCA, ADAS-cog, and DSST). (Figure 2)
·Figure1
·Figure2
Conclusions:
Different influential factors and cognition are associated with different glymphatic markers, including DTI-ALPS, FW fraction, and plasma GFAP.
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 1
Physiology, Metabolism and Neurotransmission:
Neurophysiology of Imaging Signals 2
Keywords:
Aging
Cellular
Cognition
Neurological
White Matter
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
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Provide references using APA citation style.
Hsu, C.-C. H., et al. (2022). "Integrated Diffusion Image Operator (iDIO): A tool for automated configuration and processing of diffusion MRI data." bioarxiv.
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Pasternak, O., et al. (2014). The Estimation of Free-Water Corrected Diffusion Tensors. Visualization and Processing of Tensors and Higher Order Descriptors for Multi-Valued Data, Berlin, Heidelberg, Springer Berlin Heidelberg.
Pasternak, O., et al. (2009). "Free water elimination and mapping from diffusion MRI." Magn Reson Med 62(3): 717-730.
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." Jpn J Radiol 35(4): 172-178.
Wei, Y. C., et al. (2023). "Vascular risk factors and astrocytic marker for the glymphatic system activity." Radiol Med 128(9): 1148-1161.