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Micro\u2010CT offers non\u2010destructive 3D imaging, yet conventional contrast agents can compromise tissue integrity and downstream analyses. This study establishes a resource\u2010efficient multimodal workflow that enables high\u2010quality imaging and subsequent histological and molecular testing from the same specimen. FFPE normal and cirrhotic liver tissues (\n                    <jats:italic>n<\/jats:italic>\n                    = 3 each) undergo an optimized micro\u2010CT protocol: DPBS wash, 30% eosin incubation, dehydration, snap\u2010freezing, and lyophilization. After imaging, tissues are rehydrated, re\u2010embedded in paraffin, and processed for routine histology, immunohistochemistry, RNA extraction with qPCR, and targeted NGS (800\u2010gene panel). The protocol yields high\u2010contrast, artifact\u2010free micro\u2010CT images with clear visualization of nuclei, sinusoidal networks, portal structures, and fibrotic septa (\u223c20x\u201340x optical equivalent). Volumetrics show minimal fibrosis in normal liver (2.8%) versus extensive remodeling in cirrhosis (43.5%). Morphology and antigenicity are preserved (H&amp;E, PSR, IHC). RNA quality supports qPCR, revealing upregulation of inflammatory and cirrhosis\u2010related genes in cirrhosis. Targeted NGS libraries are successfully generated, with protocol\u2010dependent performance differences. This minimally destructive workflow maximizes information yield from limited tissue, enabling integrated imaging and molecular profiling with broad utility in pathology, biobanking, and translational research.\n                  <\/jats:p>","DOI":"10.1002\/advs.77406","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T06:40:59Z","timestamp":1787985659000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Optimized Freeze\u2010Dry Multimodal Workflow for Sequential Micro\u2010CT Imaging, Histology, and Molecular Profiling: A Use Case in Human Liver Fibrosis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3027-8164","authenticated-orcid":false,"given":"Kristijan","family":"Skok","sequence":"first","affiliation":[{"name":"Diagnostic and Research Institute of Pathology Medical University of Graz  Graz Austria"},{"name":"Institute of Biomedical Sciences, 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Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R.","family":"Wanless","sequence":"additional","affiliation":[{"name":"Department of Pathology, Queen Elizabeth II Health Sciences Centre Dalhousie University  Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-3786","authenticated-orcid":false,"given":"Uro\u0161","family":"Maver","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Faculty of Medicine University of Maribor  Maribor Slovenia"},{"name":"University of Maribor Faculty of Medicine Department of Pharmacology  Maribor Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9105-106X","authenticated-orcid":false,"given":"Katrin","family":"Panzitt","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Institute of Pathology Medical University of Graz  Graz 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