Individualised mapping of living human brain mitochondria by MRI reveals signatures of bioenergetic defects.

Overview

1. Brain Connectivity and Behaviour Laboratory, Bordeaux, France; Groupe d'Imagerie Neurofonctionnelle, Institut des Maladies Neurodégénératives-UMR 5293, CNRS, CEA University of Bordeaux, France
2. Department of Psychiatry, Divisions of Molecular Therapeutics and Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, USA
3. Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, United States
4. New York State Psychiatric Institute, New York, NY, USA
5. Robert N Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, NY, USA

Abstract

Mitochondria power brain function and cognition, yet no label-free, non-invasive method has existed to explore their relationship to ageing, disease, and cognition in humans. The MitoBrainMap framework predicts mitochondrial features from magnetic resonance data alone, potentially bridging cellular biology with macroscale brain organization. Here we tested whether it captures meaningful age- and disease-related variation across individuals. MR-predicted mitochondrial density and tissue respiratory capacity declined with age, whereas intrinsic mitochondrial respiratory capacity was relatively preserved. Correlations among predicted features matched known mitochondrial biology, supporting preliminary construct validity. In patients with genetically confirmed mitochondrial diseases, predicted maps revealed region-specific alterations, notably the expected compensatory upregulation of nuclear- encoded complex II. Predicted features were further associated with the energetic stress marker GDF15 and with cognitive performance, linking brain mitochondrial estimates to systemic physiology and behavior. These findings introduce a first-generation, label-free neuroimaging-based mitochondrial mapping as a non-invasive window into living human brain mitochondria.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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Data and Code Availability Statement

The MiSBIE study protocol is available and data can be requested at www.picardlab.com/MiSBIE.

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Version 2, 28 September 2026

• Language: n/a → en

Version 1, 27 September 2026: the first record

Recorded: type, journal, dates, 7 authors, 1 funder, 69 references.

Cite

This paper

de Schotten, M. T., Liu, C. C., Kelly, C., Bo, K., Wager, T. D., Mosharov, E. V., & Picard, M. (2026). Individualised mapping of living human brain mitochondria by MRI reveals signatures of bioenergetic defects. Research Square (preprint). https://doi.org/10.21203/rs.3.rs-10117408/v1

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