Abstract

Diffusion tensor imaging (DTI), which is a technique for measuring the degree and direction of movement of water molecules in tissue, has been widely used to noninvasively assess white matter (WM) or gray matter (GM) microstructures in vivo. Mean diffusivity (MD), which is the average diffusion across all directions, has been considered as a marker of WM tract degeneration or extracellular space enlargement in GM. Recent lines of evidence suggest that cortical MD can better identify early-stage Alzheimer's disease than structural morphometric parameters in magnetic resonance imaging. However, knowledge of the relationships between cortical MD and other biological factors in the same cortical region, e.g. metabolites, is still limited. Thirty-three healthy elderly individuals [aged 50-77 years (mean, 63.8±7.4 years); 11 males and 22 females] were enrolled. We estimated the associations between cortical MD and neurotransmitter levels. Specifically, we measured levels of γ-aminobutyric acid (GABA) and glutamate + glutamine (Glx), which are inhibitory and excitatory neurotransmitters, respectively, in medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) using MEGA-PRESS magnetic resonance spectroscopy, and we measured regional cortical MD using DTI. Cortical MD was significantly negatively associated with Glx levels in both mPFC and PCC. No significant association was observed between cortical MD and GABA levels in either GM region. Our findings suggest that degeneration of microstructural organization in GM, as determined on the basis of cortical MD measured by DTI, is accompanied by the decline of Glx metabolism within the same GM region.

Highlights

  • Over the last 30 years, various methods of magnetic resonance imaging (MRI) have been developed and used to assess brain alterations associated with normal aging and aged-related neurodegenerative diseases, such as mild cognitive impairment and Alzheimer’s disease (Elman et al, 2017)

  • In this study of healthy elderly people without dementia, we examined the associations between cortical Mean diffusivity (MD) and the levels of γ-aminobutyric acid (GABA) and glutamine + glutamate (Glx), which are inhibitory and excitatory neurotransmitters, respectively, in the medial prefrontal cortex and posterior cingulate cortex (PCC) by Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) using MEGA-PRESS (Bauer et al, 2013; Jocham et al, 2012)

  • The MD in medial prefrontal cortex (mPFC) or PCC did not correlate with Cr level in each volume of interest (VOI), respectively

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Summary

Introduction

Over the last 30 years, various methods of magnetic resonance imaging (MRI) have been developed and used to assess brain alterations associated with normal aging and aged-related neurodegenerative diseases, such as mild cognitive impairment and Alzheimer’s disease (Elman et al, 2017). Many previous DTI studies have revealed altered FA and MD even in normal aging (Abe et al, 2008; Benedetti et al, 2006; Garcia-Lazaro et al, 2016), age-related neurodegenerative diseases, such as mild cognitive impairment and Alzheimer’s disease (Nesteruk et al, 2016; Nishioka et al, 2015), demyelinating diseases, such as multiple sclerosis (de Kouchkovsky et al, 2016), and neuropsychiatric diseases, such as depression and schizophrenia (Jiang et al, 2017; Singh et al, 2016) Most of these studies have focused on WM or deep GM such as the hippocampus, because these brain regions have high directionality in water diffusion (Manna et al, 2015; Ziyan and Westin, 2008), whereas water diffusion in the cerebral cortex has an isotropic direction at the level of conventional DTI resolution (Elman et al, 2017). Knowledge of the relationships between cortical MD and other biological factors in the same cortical region, e.g. metabolites, is still limited

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