Predictive value of brain 18F-FDG PET neuroimaging in a mouse model of sudden death

Marcos-Macias, E.; Godoy-Corchuelo, J. M.; Fernandez de la Rosa, R.; Guaman-Chulunchana, M. E.; Garcia-Martin, A.; Fonseca Lemos de Oliveira, L.; Dias de Brito Oliveira, R.; de Francisco Magnani, E.; Pozo, M. A.; Garcia-Garcia, L.; Brackhan, M.; Corrochano, S.; Bascunana, P.

doi:10.64898/2026.09.14.751341

bioRxiv · 10.64898/2026.09.14.751341

Predictive value of brain 18F-FDG PET neuroimaging in a mouse model of sudden death

Marcos-Macias, E.·Godoy-Corchuelo, J. M.·Fernandez de la Rosa, R.·Guaman-Chulunchana, M. E.·Garcia-Martin, A.·Fonseca Lemos de Oliveira, L.·Dias de Brito Oliveira, R.·de Francisco Magnani, E.·Pozo, M. A.·Garcia-Garcia, L.·Brackhan, M.·Corrochano, S.·Bascunana, P.

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Abstract

Sudden unexpected death (SUD) is a major cause of mortality in neurological disorders, with poorly understood mechanisms and no reliable biomarkers. Brain-heart axis dysfunction has been implicated in SUD pathogenesis. Using the FUSdelta14 mouse model, we tested whether cerebral glucometabolism, assessed by 18F-FDG PET, reflects autonomic dysregulation and predicts SUD vulnerability. 18F-FDG PET/CT and ECG were acquired at 10 weeks of age (FUSdelta14/delta14 n=12, FUS+/delta14 n=14, FUS+/+ n=12). Heart rate variability was analyzed in time and frequency domains, brain uptake via volume of interest and voxel-wise approaches, and correlations assessed by Pearson's analysis. A classification-tree model tested SUD predictability within the FUSdelta14/delta14 group. Female FUSdelta14/delta14 mice showed reduced 18-FFDG uptake in basal forebrain septum, left amygdala, and brainstem, with increased uptake in hypothalamus and right midbrain, alongside cardiac size, metabolic and heart rate variability alterations. 50% experienced SUD; in this subgroup, PET showed cortical hypometabolism (insular, entorhinal) and hypermetabolism in hypothalamus, amygdala, septum, and brainstem. Although brainstem uptake was able to singlehandedly predict SUD in this particular FUSdelta14/delta14 group (AUC=0.787), cross-validation also highlighted cortical metabolism as a relevant feature (UsageRate=0.38 and 0.44, respectively). 18F-FDG PET identifies region-specific metabolic signatures of brain-heart axis dysfunction linked to SUD, supporting its potential as a non-invasive biomarker for risk stratification.

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Marcos-Macias, E., Godoy-Corchuelo, J. M., Fernandez de la Rosa, R., Guaman-Chulunchana, M. E., Garcia-Martin, A., Fonseca Lemos de Oliveira, L., Dias de Brito Oliveira, R., de Francisco Magnani, E., Pozo, M. A., Garcia-Garcia, L., Brackhan, M., Corrochano, S., Bascunana, P.. 2026-09-21. Predictive value of brain 18F-FDG PET neuroimaging in a mouse model of sudden death. https://doi.org/10.64898/2026.09.14.751341

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