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Epileptogenesis was induced with lateral fluid percussion\u2010induced traumatic brain injury (TBI) in adult male Sprague Dawley rats. In the EPITARGET cohort, \u2010weighted MRI was performed at 2, 7, and 21\u00a0days and in the EpiBioS4Rx cohort at 2, 9, and 30\u00a0days and 5\u00a0months post\u2010TBI. Both hippocampi were segmented using convolutional neural networks. The extracted segmentation mask was used for a geometric construction, extracting 39 parameters that described the position and orientation of the left and right hippocampus. In each cohort, we assessed the parameters as prognostic biomarkers for posttraumatic epilepsy (PTE) both individually, using repeated measures analysis of variance, and in combination, using random forest classifiers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The extracted parameters were highly effective in discriminating between sham\u2010operated and TBI rats in both the EPITARGET and EpiBioS4Rx cohorts at all timepoints (t; balanced accuracy &gt; .9). The most discriminating parameter was the inclination of the hippocampus ipsilateral to the lesion at <jats:italic>t<\/jats:italic>\u00a0=\u00a02 days and the volumes at <jats:italic>t\u00a0<\/jats:italic>\u2265\u00a07 days after TBI. Furthermore, in the EpiBioS4Rx cohort, we could effectively discriminate epileptogenic from nonepileptogenic animals with a longer MRI follow\u2010up, at <jats:italic>t<\/jats:italic>\u00a0=\u00a0150 days (area under the curve\u00a0=\u00a0.78, balanced accuracy\u00a0=\u00a0.80, <jats:italic>p\u00a0<\/jats:italic>=\u00a0.0050), based on the orientation of both hippocampi. We found that the ipsilateral hippocampus rotated outward on the horizontal plane, whereas the contralateral hippocampus rotated away from the vertical direction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>We demonstrate that assessment of TBI\u2010induced hippocampal deformation by clinically translatable MRI methodologies detects subjects with prior TBI as well as those at high risk of PTE, paving the way toward subject stratification for antiepileptogenesis studies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17264","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T09:37:29Z","timestamp":1650620249000},"page":"1849-1861","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hippocampal position and orientation as prognostic biomarkers for posttraumatic epileptogenesis: An experimental study in a rat lateral fluid percussion model"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7510-1058","authenticated-orcid":false,"given":"Riccardo","family":"De Feo","sequence":"first","affiliation":[{"name":"A. 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