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However, it has a limited ability to detect subtle alterations in hippocampal morphometry. Here, we establish and apply a novel geometry\u2010based tool that enables point\u2010wise morphometric analysis based on an intrinsic coordinate system of the hippocampus. We hypothesized that this point\u2010wise analysis uncovers structural alterations not measurable by volumetry, but associated with histological underpinnings and the neuropsychological profile of mTLE. We conducted a retrospective study in 204 individuals with mTLE and 57 age\u2010 and gender\u2010matched healthy subjects. FreeSurfer\u2010based segmentations of hippocampal subfields in 3T\u2010MRI were subjected to a geometry\u2010based analysis that resulted in a coordinate system of the hippocampal mid\u2010surface and allowed for point\u2010wise measurements of hippocampal thickness and other features. Using point\u2010wise analysis, we found significantly lower thickness and higher FLAIR signal intensity in the entire affected hippocampus of individuals with hippocampal sclerosis (HS\u2010mTLE). In the contralateral hippocampus of HS\u2010mTLE and the affected hippocampus of MRI\u2010negative mTLE, we observed significantly lower thickness in the presubiculum. Impaired verbal memory was associated with lower thickness in the left presubiculum. In HS\u2010mTLE histological subtype 3, we observed higher curvature than in subtypes 1 and 2 (all <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). These findings could not be observed using conventional volumetry (Bonferroni\u2010corrected <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.05). We show that point\u2010wise measures of hippocampal morphometry can uncover structural alterations not measurable by volumetry while also reflecting histological underpinnings and verbal memory. This substantiates the prospect of their clinical application.<\/jats:p>","DOI":"10.1002\/hbm.26392","type":"journal-article","created":{"date-parts":[[2023,6,24]],"date-time":"2023-06-24T21:38:15Z","timestamp":1687642695000},"page":"4467-4479","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel geometry\u2010based analysis of hippocampal morphometry in mesial temporal lobe epilepsy"],"prefix":"10.1002","volume":"44","author":[{"given":"Laura","family":"Fischbach","sequence":"first","affiliation":[{"name":"Department of Epileptology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0555-6214","authenticated-orcid":false,"given":"Tobias","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Epileptology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kersten","family":"Diers","sequence":"additional","affiliation":[{"name":"AI in Medical Imaging German Center for Neurodegenerative Diseases (DZNE)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juri\u2010Alexander","family":"Witt","sequence":"additional","affiliation":[{"name":"Department of Epileptology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Brugues","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeri","family":"Borger","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Schidlowski","sequence":"additional","affiliation":[{"name":"Department of Epileptology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"R\u00e1cz","sequence":"additional","affiliation":[{"name":"Department of Epileptology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Baumgartner","sequence":"additional","affiliation":[{"name":"Department of Epileptology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randi","family":"von Wrede","sequence":"additional","affiliation":[{"name":"Department of Epileptology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Paech","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute of Experimental Epileptology and Cognition Research University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Radbruch","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Vatter","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert J.","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010J\u00fcrgen","family":"Huppertz","sequence":"additional","affiliation":[{"name":"Swiss Epilepsy Clinic Klinik Lengg AG  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Helmstaedter","sequence":"additional","affiliation":[{"name":"Department of Epileptology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Surges","sequence":"additional","affiliation":[{"name":"Department of Epileptology University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Reuter","sequence":"additional","affiliation":[{"name":"AI in Medical Imaging German Center for Neurodegenerative Diseases (DZNE)  Bonn Germany"},{"name":"Athinoula A. 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