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The NextBrain histological atlas was recently introduced to support such fine-grained investigations, but its existing Bayesian segmentation framework remains computationally prohibitive, particularly for large-scale studies. We present a new, open-source tool that dramatically accelerates segmentation using a hybrid approach combining: machine learning, contrast-adaptive segmentation; target-specific image synthesis; and fast diffeomorphic registration (all three with GPU support). Our method enables highly granular segmentation of brain MRI scans of any resolution and contrast (in vivo or ex vivo) at a fraction of the computational cost of the original method (&amp;lt;5 minutes on a GPU). We validate our tool on four different modalities (in vivo MRI, ex vivo MRI, HiP-CT, and photography) across a total of approximately 4,000 brain scans. Our results demonstrate that the accelerated approach achieves comparable accuracy to the original method in terms of Dice scores, while reducing runtime by over an order of magnitude. This work enables high-resolution anatomical analysis at unprecedented scale and flexibility, providing a practical solution for large neuroimaging studies. Our tool is publicly available in FreeSurfer (https:\/\/surfer.nmr.mgh.harvard.edu\/fswiki\/HistoAtlasSegmentation).<\/jats:p>","DOI":"10.1162\/imag.a.1244","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T20:01:21Z","timestamp":1777406481000},"update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":1,"title":["Fast segmentation with the NextBrain histological atlas"],"prefix":"10.1162","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3186-244X","authenticated-orcid":false,"given":"Oula","family":"Puonti","sequence":"first","affiliation":[{"name":"Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital \u2013 Amager and Hvidovre, Copenhagen, Denmark"},{"name":"Athinoula A. 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