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However, although the cerebellum was suggested to be more severely undersized than the rest of the brain, it has not yet been given a specific place in the FASD diagnostic criteria where neuroanatomical features still count for little if anything in diagnostic specificity. We applied a combination of cerebellar segmentation tools on a 1.5\u2009T 3DT1 brain MRI dataset from a monocentric population of 89 FASD (52 FAS, 37 NS\u2010FASD) and 126 typically developing controls (6\u201320\u2009years old), providing 8 volumes: cerebellum, vermis and 3 lobes (anterior, posterior, inferior), plus total brain volume. After adjustment of confounders, the allometric scaling relationship between these cerebellar volumes (V<jats:sub>i<\/jats:sub>) and the total brain or cerebellum volume (V<jats:sub>t<\/jats:sub>) was fitted (V<jats:sub>i<\/jats:sub>\u2009=\u2009bV<jats:sub>t<\/jats:sub><jats:sup>a<\/jats:sup>), and the effect of group (FAS, control) on allometric scaling was evaluated. We then estimated for each cerebellar volume in the FAS population the deviation from the typical scaling (<jats:sub>v<\/jats:sub>DTS) learned in the controls. Lastly, we trained and tested two classifiers to discriminate FAS from controls, one based on the total cerebellum <jats:sub>v<\/jats:sub>DTS only, the other based on all the cerebellar <jats:sub>v<\/jats:sub>DTS, comparing their performance both in the FAS and the NS\u2010FASD group. Allometric scaling was significantly different between FAS and control group for all the cerebellar volumes (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001). We confirmed the excess of total cerebellum volume deficit (<jats:sub>v<\/jats:sub>DTS\u2009=\u2009\u221210.6%) and revealed an antero\u2010inferior\u2010posterior gradient of volumetric undersizing in the hemispheres (\u221212.4%, 1.1%, 2.0%, respectively) and the vermis (\u221216.7%, \u22129.2%, \u22128.6%, repectively). The classifier based on the intracerebellar gradient of <jats:sub>v<\/jats:sub>DTS performed more efficiently than the one based on total cerebellum <jats:sub>v<\/jats:sub>DTS only (AUC\u2009=\u200992% vs. 82%, <jats:italic>p<\/jats:italic>\u2009=\u2009.001). Setting a high probability threshold for &gt;95% specificity of the classifiers, the gradient\u2010based classifier identified 35% of the NS\u2010FASD to have a FAS cerebellar phenotype, compared to 11% with the cerebellum\u2010only classifier (<jats:italic>p<\/jats:italic><jats:sub>FISHER<\/jats:sub>\u2009=\u20090.027). In a large series of FASD, this study details the volumetric undersizing within the cerebellum at the lobar and vermian level using allometric scaling, revealing an anterior\u2010inferior\u2010posterior gradient of vulnerability to prenatal alcohol exposure. It also strongly suggests that this intracerebellar gradient of volumetric undersizing may be a reliable neuroanatomical signature of FAS that could be used to improve the specificity of the diagnosis of NS\u2010FASD.<\/jats:p>","DOI":"10.1002\/hbm.26348","type":"journal-article","created":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T18:14:01Z","timestamp":1684606441000},"page":"4321-4336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Enhancing fetal alcohol spectrum disorders diagnosis with a classifier based on the intracerebellar gradient of volumetric undersizing"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6434-7992","authenticated-orcid":false,"given":"Justine","family":"Fraize","sequence":"first","affiliation":[{"name":"CEA Paris\u2010Saclay, Joliot Institute, NeuroSpin, UNIACT, Centre d'\u00e9tudes de Saclay  Gif\u2010sur\u2010Yvette 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