Age-trajectories of higher-order diffusion properties of major brain metabolites in cerebral and cerebellar grey matter using in vivo diffusion-weighted MR spectroscopy at 3T

Simsek, Kadir, Gallea, Cécile, Genovese, Guglielmo, Lehéricy, Stephane, Branzoli, Francesca and Palombo, Marco ORCID: https://orcid.org/0000-0003-4892-7967 2025. Age-trajectories of higher-order diffusion properties of major brain metabolites in cerebral and cerebellar grey matter using in vivo diffusion-weighted MR spectroscopy at 3T. Aging Cell , e14477. 10.1111/acel.14477

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Abstract

Healthy brain aging involves changes in both brain structure and function, including alterations in cellular composition and microstructure across brain regions. Unlike diffusion-weighted MRI (dMRI), diffusion-weighted MR spectroscopy (dMRS) can assess cell-type specific microstructural changes, providing indirect information on both cell composition and microstructure through the quantification and interpretation of metabolites' diffusion properties. This work investigates age-related changes in the higher-order diffusion properties of total N-Acetyl-aspartate (neuronal biomarker), total choline (glial biomarker), and total creatine (both neuronal and glial biomarker) beyond the classical apparent diffusion coefficient in cerebral and cerebellar gray matter of healthy human brain. Twenty-five subjects were recruited and scanned using a diffusion-weighted semi-LASER sequence in two brain regions-of-interest (ROI) at 3T: posterior-cingulate (PCC) and cerebellar cortices. Metabolites' diffusion was characterized by quantifying metrics from both Gaussian and non-Gaussian signal representations and biophysical models. All studied metabolites exhibited lower apparent diffusivities and higher apparent kurtosis values in the cerebellum compared to the PCC, likely stemming from the higher microstructural complexity of cellular composition in the cerebellum. Multivariate regression analysis (accounting for ROI tissue composition as a covariate) showed slight decrease (or no change) of all metabolites' diffusivities and slight increase of all metabolites' kurtosis with age, none of which statistically significant (p > 0.05). The proposed age-trajectories provide benchmarks for identifying anomalies in the diffusion properties of major brain metabolites which could be related to pathological mechanisms altering both the brain microstructure and cellular composition.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Psychology Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher:	Wiley Open Access
ISSN:	1474-9718
Date of First Compliant Deposit:	6 January 2025
Date of Acceptance:	20 December 2024
Last Modified:	06 Feb 2025 14:28
URI:	https://orca.cardiff.ac.uk/id/eprint/175036

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