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BRIEF RESEARCH REPORT article

Front. Aging Neurosci.
Sec. Cellular and Molecular Mechanisms of Brain-aging
Volume 16 - 2024 | doi: 10.3389/fnagi.2024.1535158

Mapping hippocampal glutamate in healthy aging with in vivo glutamate-weighted CEST (GluCEST) imaging

Provisionally accepted
Maggie K Pecsok Maggie K Pecsok 1,2Heather Robinson Heather Robinson 3*Ally Atkins Ally Atkins 2Monica E Calkins Monica E Calkins 2,4*Mark A Elliot Mark A Elliot 5*Arianna Mordy Arianna Mordy 6*Jacqueline Stifelman Jacqueline Stifelman 2*Ruben Gur Ruben Gur 2,7Paul J Moberg Paul J Moberg 2*Ravi Prakash Reddy Nanga Ravi Prakash Reddy Nanga 5Kosha Ruparel Kosha Ruparel 2,4*Russel T Shinohara Russel T Shinohara 8*David A Wolk David A Wolk 9*Ravinder Reddy Ravinder Reddy 5*David R Roalf David R Roalf 2,7*
  • 1 University of Pennsylvania, Philadelphia, United States
  • 2 Brain Behavior Laboratory, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • 3 Department of Psychological Sciences, Institute for the Brain and Cognitive Sciences, University of Connecticut, Storrs, CT, United States
  • 4 Lifespan Brain Institute, Children’s Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, United States
  • 5 Center for Advanced Metabolic Imaging in Precision Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
  • 6 Cognitive and Clinical Neuroscience Lab, UCLA Brain Mapping Center, Department of Psychiatry and Behavioral Sciences, University of California, Los Angeles,, Los Angeles, United States
  • 7 Department of Child and Adolescent Psychiatry and Behavioral Sciences, Lifespan Brain Institute, Children’s Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, United States
  • 8 Penn Statistics in Imaging and Visualization Endeavor, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
  • 9 Penn Memory Center, University of Pennsylvania Health System, Philadelphia, Pennsylvania, United States

The final, formatted version of the article will be published soon.

    Introduction: Hippocampal glutamate (Glu) dysfunction is a pertinent indicator of neurodegeneration, yet mapping typical age-related changes in Glu has been challenging. Here, we use a 7T MRI approach, Glutamate Chemical Exchange Saturation Transfer (GluCEST), to measure bilateral hippocampal Glu in healthy old (HOA) and young (HYA) adults.Methods: Bilateral hippocampal GluCEST data was acquired from 27 HOA and 22 HYA using 7T MRI. GluCEST differences by age and hemisphere were tested with a linear mixed model. GluCEST asymmetry index was also evaluated by age. Exploratory analyses examined associations between hippocampal GluCEST, age group, and scores on the Montreal Cognitive Assessment (MoCA) and Cognitive Complaints Index (CCI).Results: GluCEST levels showed an age group and hemisphere interaction. In HOA, GluCEST was higher in left than right hippocampus, but in HYA, GluCEST level was equivalent across hemispheres. HOA had lower GluCEST than HYA in the right hippocampus. GluCEST asymmetry index confirmed significant left asymmetry in HOA. Lower GluCEST levels in HOA were associated with subjective cognitive complaints as measured by the CCI.Discussion: Hippocampal GluCEST provides insight into age-related neural changes, with lower GluCEST in the right hippocampus in older adults. These findings offer a step towards elucidating the asymmetrical trajectory of hippocampal glutamatergic alterations and their relationship to cognitive phenotypes.

    Keywords: Glutamate, Aging, 7Tesla MRI, GluCEST, Hippocampus

    Received: 26 Nov 2024; Accepted: 31 Dec 2024.

    Copyright: © 2024 Pecsok, Robinson, Atkins, Calkins, Elliot, Mordy, Stifelman, Gur, Moberg, Nanga, Ruparel, Shinohara, Wolk, Reddy and Roalf. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Heather Robinson, Department of Psychological Sciences, Institute for the Brain and Cognitive Sciences, University of Connecticut, Storrs, CT, United States
    Monica E Calkins, Brain Behavior Laboratory, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, United States
    Mark A Elliot, Center for Advanced Metabolic Imaging in Precision Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, United States
    Arianna Mordy, Cognitive and Clinical Neuroscience Lab, UCLA Brain Mapping Center, Department of Psychiatry and Behavioral Sciences, University of California, Los Angeles,, Los Angeles, United States
    Jacqueline Stifelman, Brain Behavior Laboratory, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, United States
    Paul J Moberg, Brain Behavior Laboratory, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, United States
    Kosha Ruparel, Brain Behavior Laboratory, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, United States
    Russel T Shinohara, Penn Statistics in Imaging and Visualization Endeavor, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
    David A Wolk, Penn Memory Center, University of Pennsylvania Health System, Philadelphia, PA 19104, Pennsylvania, United States
    Ravinder Reddy, Center for Advanced Metabolic Imaging in Precision Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, United States
    David R Roalf, Brain Behavior Laboratory, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.