Academic Journal
In Vivo 4D Oxy-Wavelet MRI as a Non-Invasive Biomarker of Brain Mitochondrial Function across the Lifespan.
| Τίτλος: | In Vivo 4D Oxy-Wavelet MRI as a Non-Invasive Biomarker of Brain Mitochondrial Function across the Lifespan. |
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| Συγγραφείς: | Cortes DRE; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA.; Animal Imaging Core, Rangos Research Center at UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA., Hartwick S; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Animal Imaging Core, Rangos Research Center at UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA., Becker-Szurszewski T; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Animal Imaging Core, Rangos Research Center at UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA., Schwab KE; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Animal Imaging Core, Rangos Research Center at UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA., Ruck C; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA., Manzoor S; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Coulson NW; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., West D; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Stapleton MC; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Wyman S; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Lo CW; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Bharathi S; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Goetzman ES; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Christodoulou AG; Department of Radiological Sciences, David Geffen School of Medicine, at UCLA, Los Angeles, CA, USA.; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA., Wu YL; Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA.; Animal Imaging Core, Rangos Research Center at UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA. |
| Πηγή: | BioRxiv : the preprint server for biology [bioRxiv] 2026 May 23. Date of Electronic Publication: 2026 May 23. |
| Τύπος έκδοσης: | Journal Article; Preprint |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| Περίληψη: | Mitochondria are essential for cellular energy production and are particularly critical for brain development and function. Neurons rely predominantly on oxidative phosphorylation for energy production, rendering the brain highly vulnerable to mitochondrial dysfunction. Consequently, impaired mitochondrial function contributes to a broad spectrum of neurological and systemic disorders, making mitochondria attractive therapeutic targets. Despite this importance, there is currently no non-invasive, spatially resolved method to assess mitochondrial function in the intact living brain. Here, we establish a non-invasive functional MRI approach-4D Oxy-wavelet MRI-to probe in vivo mitochondrial electron transport chain (ETC) function in a spatially specific manner across the lifespan, from fetal to adult brains. This method employs a low-rank k-t sub-Nyquist acquisition strategy to achieve simultaneous structural and functional imaging with high spatial (78 μm) and temporal (~14 ms) resolution, enabling motion-robust imaging in multi-fetal mouse pregnancies. Mitochondrial ETC function is interrogated by measuring oxygen homeostasis responses to brief hypoxic challenges, analyzed using computational time-frequency wavelet profiling. We validate this approach in mouse models of mitochondrial respiratory chain disease and late-onset Alzheimer's disease, from in utero fetuses to adults, and demonstrate reproducibility and specificity using pharmacological hyperemia and ETC complex I inhibition. We further show parallel wavelet responses in placenta and fetal brain, enabling multi-organ interrogation of the placenta-brain axis. Finally, we present first-in-human feasibility data, supporting translational potential for non-invasive assessment of mitochondrial function in living brains across the lifespan. |
| Competing Interests: | Declaration of Competing Interests The authors declare they have no competing interests to disclose in regards to the work contained within this submission. |
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| Grant Information: | R21 EB023507 United States EB NIBIB NIH HHS; R21 NS121706 United States NS NINDS NIH HHS; R21 NS142555 United States NS NINDS NIH HHS |
| Contributed Indexing: | Keywords: Mitochondria; brain; fMRI; fetal; low-rank reconstruction; wavelet analysis |
| Entry Date(s): | Date Created: 20260604 Date Completed: 20260623 Latest Revision: 20260923 |
| Update Code: | 20260923 |
| PubMed Central ID: | PMC13228471 |
| DOI: | 10.64898/2026.05.21.726892 |
| PMID: | 42239271 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2692-8205 |
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| DOI: | 10.64898/2026.05.21.726892 |