Probing Mitochondrial Function in Intact Fetal Brains with Ungated 4D Oxy-wavelet MRI in an Irradiation Injury Mouse Model
Anthony Christodoulou1, Margaret Caroline Stapleton2, Devin Raine Everaldo Cortes3, Eric Goetzman4, Cecilia Lo2, Michael Epperly 5, Joel Greenberger 5, and Yijen L Wu2
1Cedars Sinai Medical Center, Los Angeles, CA, United States, 2Developmental Biology, University of Pittsburgh, Pittsburgh, PA, United States, 3Biomedical Engineering, University of Pittsburgh, Pittsburgh, PA, United States, 4Pediatrics, University of Pittsburgh, Pittsburgh, PA, United States, 5Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, United States
A novel motion-and-time resolved 4D oxy-wavelet MRI (4D-fMRI acquired with oscillating hypoxia challenges, analyzed by a continuous wavelet transform mimicking experimental oscillations) can acquire fetal MRI with high spatiotemporal resolution and can probe mitochondrial functions in live fetal brains. 4D oxy-wavelet MRI outcomes were validated with Oroboros mitochondrial function assays and correlated with mitochondrial targeting drug JP4-039 in a fetal irradiation injury mouse model. The mouse fetuses showed poor 4D oxy-wavelet outcomes had poor mitochondrial functions and vice versa. Furthermore, an automated time-frequency analysis scheme can correctly differentiate normal vs irradiated fetuses, paving the way for future AI-based automatic diagnosis.
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