{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:15:16Z","timestamp":1785428116632,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,23]]},"group-title":"Bioengineering","reference-count":113,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["EB023507"],"award-info":[{"award-number":["EB023507"]}]},{"name":"NIH","award":["NS121706"],"award-info":[{"award-number":["NS121706"]}]},{"name":"NIH","award":["NS142555"],"award-info":[{"award-number":["NS142555"]}]},{"award":["18CDA34140024"],"award-info":[{"award-number":["18CDA34140024"]}],"id":[{"id":"https:\/\/ror.org\/013kjyp64","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"United States Department of Defense","doi-asserted-by":"crossref","award":["W81XWH1810070"],"award-info":[{"award-number":["W81XWH1810070"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000005","name":"United States Department of Defense","doi-asserted-by":"crossref","award":["W81XWH-22-1-0221"],"award-info":[{"award-number":["W81XWH-22-1-0221"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>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.<\/jats:p>\n                <jats:p>\n                  Here, we establish a non-invasive functional MRI approach\u20144D Oxy-wavelet MRI\u2014to 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\n                  <jats:italic>k<\/jats:italic>\n                  -t sub-Nyquist acquisition strategy to achieve simultaneous structural and functional imaging with high spatial (78 \u03bcm) and temporal (\u223c14 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.\n                <\/jats:p>\n                <jats:p>\n                  We validate this approach in mouse models of mitochondrial respiratory chain disease and late-onset Alzheimer\u2019s disease, from\n                  <jats:italic>in utero<\/jats:italic>\n                  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\u2013brain 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.\n                <\/jats:p>","DOI":"10.64898\/2026.05.21.726892","type":"posted-content","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T11:25:13Z","timestamp":1779535513000},"source":"Crossref","is-referenced-by-count":0,"title":["In Vivo 4D Oxy-Wavelet MRI as a Non-Invasive Biomarker of Brain Mitochondrial Function across the Lifespan"],"prefix":"10.64898","author":[{"given":"Devin Raine Everaldo","family":"Cortes","sequence":"first","affiliation":[{"name":"Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA"},{"name":"Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA"},{"name":"Animal Imaging Core, Rangos Research Center at UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA, 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