Aldehydic load as an objective imaging biomarker of mild traumatic brain injury

Alexia Kirby; Cian Ward; Clara S Goulet; Nicholas D Calvert; Ryan Daniel; Joseph Wai-Hin Leung; Ashwin Sharma; Mojmír Suchý; Cassandra Donatelli; Jing Wang; Emily Standen; Adam J Shuhendler

doi:10.1038/s44303-025-00096-w

Aldehydic load as an objective imaging biomarker of mild traumatic brain injury

Npj Imaging. 2025 Jun 26;3(1):30. doi: 10.1038/s44303-025-00096-w.

Authors

Alexia Kirby^{1

2}, Cian Ward¹, Clara S Goulet¹, Nicholas D Calvert^{2

3}, Ryan Daniel¹, Joseph Wai-Hin Leung^{1

4}, Ashwin Sharma¹, Mojmír Suchý^{2

3}, Cassandra Donatelli¹, Jing Wang^{4

5

6}, Emily Standen¹, Adam J Shuhendler^{7

8

9

10}

Affiliations

¹ Department of Biology, University of Ottawa, Ottawa, ON, Canada.
² University of Ottawa Heart Institute, Ottawa, ON, Canada.
³ Department of Chemistry and Biomolecular Sciences; University of Ottawa, Ottawa, ON, Canada.
⁴ Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁵ Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
⁶ Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada.
⁷ Department of Biology, University of Ottawa, Ottawa, ON, Canada. adam.shuhendler@uottawa.ca.
⁸ University of Ottawa Heart Institute, Ottawa, ON, Canada. adam.shuhendler@uottawa.ca.
⁹ Department of Chemistry and Biomolecular Sciences; University of Ottawa, Ottawa, ON, Canada. adam.shuhendler@uottawa.ca.
¹⁰ Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada. adam.shuhendler@uottawa.ca.

Abstract

Mild traumatic brain injury (mTBI) is neurological impairment induced by biomechanical forces without structural brain damage, currently without an objective diagnostic tool. Downstream injury stems from oxidative damage leading to the production of neurotoxic aldehydes. A collagen-based 3D corticomimetic in vitro model of concussion was developed, confirming aldehyde production following impact. Total aldehyde levels were mapped in vivo following mTBI using a novel CEST-MRI contrast agent, ProxyNA₃, in a new model of closed-head, awake, single-impact concussion in aged and young mice with aldehyde dehydrogenase 2 (ALDH2) deficiency. ProxyNA₃-MRI was performed before impact, and on days two- and seven- post-impact. MRI signal enhancement significantly increased at two days post-injury prior to astrocyte activation at seven days post-injury. The data suggest that advanced age and ALDH2 deficiency contribute to increased aldehydic load following mTBI. Overall, ProxyNA₃ was capable of mapping concussion-associated aldehydes, supporting its application as an objective diagnostic tool for concussion.

Abstract

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